Study Evaluating Inotuzumab Ozogamicin [CMC-544] Administered In Combination With Rituximab In Subjects With Non-Hodgkin's Lymphoma (NHL)

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00299494
• Collaborator: UCB Pharma (Industry)
• Enrollment: 119
• Locations: 38
• Arms: 3
• Actual Duration (Months): 97
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of the study is to determine the tolerability, the initial safety profile and maximum tolerated dose, and to obtain preliminary information on the antitumor activity of inotuzumab ozogamicin [CMC-544] in combination with rituximab in subjects with follicular, diffuse large B-Cell, or mantle cell NHL.

Condition or Disease	Intervention/Treatment	Phase
B-Cell Lymphoma	Drug: inotuzumab ozogamicin; Drug: inotuzumab ozogamicin; Drug: inotuzumab ozogamicin; Drug: Rituximab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Non-Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study Of Cmc-544 Administered In Combination With Rituximab In Subjects With Follicular Or Diffuse Large B-cell Non-hodgkin's Lymphoma
• Actual Study Start Date: May 4, 2006
• Actual Primary Completion Date: May 19, 2014
• Actual Study Completion Date: Jun 2, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB (FOLLICULAR) Follicular	Drug: inotuzumab ozogamicin; IV, 1.8 mg/m2, q4w; Other Names: CMC-544 ; Drug: Rituximab; rituximab 375 mg/m^2 via IV infusion on Day 1
Experimental: INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB (DLBCL) Diffuse Large B-cell Lymphoma	Drug: inotuzumab ozogamicin; IV, 1.8 mg/m2, q4w; Other Names: CMC-544 ; Drug: Rituximab; rituximab 375 mg/m^2 via IV infusion on Day 1
Experimental: INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB (REFRACTORY) Refractory Aggressive NHL	Drug: inotuzumab ozogamicin; IV, 1.8 mg/m2, q4w; Other Names: CMC-544 ; Drug: Rituximab; rituximab 375 mg/m^2 via IV infusion on Day 1

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin in Combination With Rituximab (375 mg/m^2 ) [First 28-day cycle]

   Inotuzumab ozogamicin was dose escalated (3 to 6 evaluable participants enrolled per dose cohort) during the first 28 days after the first administration of inotuzumab ozogamicin + rituximab. Enrollment at the next dose level or enrollment of additional subjects into a cohort proceeded according to the following criteria: 0 dose-limiting toxicity (DLT) by Day 28 of first dose move to higher dose, 1 participant reporting DLT but no others in cohort by Day 28 of first dose move to higher dose, greater than 2 participants reporting DLT by Day 28 of first dose stop and prior dose level considered MTD. The worldwide medical monitor and investigators reviewed all significant study drug-related toxicities to determine if the dose escalation rules were satisfied and whether the dose escalation schedule required modification.

2. Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) [Protocol reporting period of from informed consent to at least 28 days after the last dose. This outcome measure time frame: From the first dose of study drug to up to 56 days after the last dose of either study drug.]

   A TEAE is any event that occurred after the first dose of study drug up to 56 days post the last dose of study drug (either rituximab or inotuzumab ozogamicin).

Secondary Outcome Measures

1. Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) [Approximately every 2 (during treatment) or 3 (during follow-up) to 6 months for up to 5 years from 1st dose]

   CR: a. Complete disappearance of all detectable clinical and radiographic evidence of disease, disease-related symptoms, and normalization of NHL assignable biochemical abnormalities ; b. lymph nodes and nodal masses must have regressed to normal size; c. Spleen regressed in size and not palpable on physical exam, size of other organs enlarged due to disease decreased in size; d. Repeat bone marrow infiltrate clear. CRu: CR but allows for a. Residual lymph node mass >1.5 cm in greatest transverse diameter has regressed by more than 75% in diameter. Individual nodes that were previously confluent regressed more than 75 % in their product diameters; b. Indeterminate bone marrow. PR: a. ≥50 % decrease in product of the diameters (SPD) of the 6 largest dominant nodes or nodal masses; b. No increase in size of other nodes, liver, or spleen, c. Liver or spleen nodules regressed ≥50% in the SPD; d. Other organs usually assessable, no measurable disease present.

2. Kaplan-Meier Estimates of Progression Free Survival (PFS) [From the date of first dose of test article until the first date on which disease progression or death was documented or new anticancer start, any of which could be reported up to 5 years post last dose]

   The Kaplan-Meier method was used to determine PFS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by >= 50% in the size of previously involved sites, c. >= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. >= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver.

3. Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months [From the first dose to 6 months after first dose]

   Progression Free Survival is defined as the time interval from the first dose of test article until the first date on which relapsed disease, progression, initiation of new anti-cancer treatment due to persistent/refractory disease, or death was documented, censored at the last tumor evaluation.

4. Kaplan-Meier Estimates of Overall Survival (OS) [From the first dose up to 5 years post last dose]

   OS was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.

5. Kaplan-Meier Estimates of the Probability of Survival at 6 Months [From the first dose to 6 months after first dose.]

   Overall Survival (OS) was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.

6. Kaplan-Meier Estimates of Time to Tumor Progression (TTP) [From the date of first dose of test article until the first date on which disease progression or death was documented, any of which could be reported up to 5 years post last dose.]

   TTP is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by >= 50% in the size of previously involved sites, c. >= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. >= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determine TTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.

7. Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months [From enrollment to up to 6 months from 1st dose.]

   Time-to-Tumor Progression (TTP): is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by >=50% in the size of previously involved sites, c. >= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. >= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determineTTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.

8. Duration of Response (CR+CRu+PR) [Time from date measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the first date relapsed disease or date of death (whichever occurs first) is objectively documented.]

   Time from date measurement criteria met for CR, CRu, or PR (whichever occurred first) until first date relapsed disease/date of death. CR: Complete disappearance of all detectable clinical, radiographic evidence of disease, disease-related symptoms, normalization of NHL assignable biochemical abnormalities; lymph nodes, nodal masses regressed to normal size; spleen size regressed, not palpable on physical exam, size of other organs enlarged due to disease. CRu: CR but allows for: residual lymph node mass >1.5 cm in greatest transverse diameter that regressed >75% in product diameter. Individual nodes previously confluent, regressed by >75% in their product diameters; Indeterminate bone marrow. PR: ≥50% decrease in SPD of 6 largest dominant nodes/nodal masses; No increase in size of other nodes, liver, or spleen; Splenic/hepatic nodules regressed by ≥50% in SPD; Except splenic/hepatic nodules, involvement of other organs assessable and no measurable disease present.

9. Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

   Serum concentration of inotuzumab ozogamicin on Dosing Days 30 and 58 were measured. AUCinf of inotuzumab ozogamicin was reported. AUCinf: AUClast (area under the serum concentration-time profile for inotuzumab ozogamicin from time zero to the time of the last quantifiable concentration) +(Clast [last quantifiable concentration]/kel [elimination rate constant]) where Clast is the predicted serum concentration of inotuzumab ozogamicin at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

10. AUClast of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUC of inotuzumab ozogamicin was reported. AUClast is area under the serum concentration-time profile from time zero to the time of the Clast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

11. Time of the Last Quantifiable Serum Concentration in a Dosing Interval (Tlast) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Tlast of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 was reported. Tlast: Time of last quantifiable concentration of inotuzumab ozogamicin. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

12. Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Steady-state serum concentrations of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUCtau of inotuzumab ozogamicin was reported. AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

13. Peak Serum Concentration (Cmax) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 were measured. Cmax of inotuzumab ozogamicin was reported. Cmax was observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

14. Time to Reach Maximum Concentration (Tmax) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

15. Average Serum Concentration at Steady State (Cav) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cav: AUCtau (Area under the concentration time profile)/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

16. Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

17. Clearance (CL) of Serum Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Clearance is defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

18. Steady-state Volume of Distribution (Vss) of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab MTD+Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Vss of inotuzumab ozogamicin on Dosing Days 30 and 58 were reported. Vss=CL*MRT (mean residence time). Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

19. MRT of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    MRT: AUMCinf/AUCinf - DOF (degrees of freedom)/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

20. Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

21. AUCinf of Total Calicheamicin (Conjugated + Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

22. AUClast of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

23. Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

24. Area Under the Steady-state Serum Concentration-time Curve (AUCtau) for Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

25. Peak Serum Concentration (Cmax) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

26. Time of Observed Maximum Concentration (Tmax) of Total Calicheamicin (Conjugated+Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

27. Average Serum Concentration (Cav) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

28. Minimum Observed Serum Trough Concentration (Cmin) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

29. Clearance (CL) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Clearance defined as Dose/AUCinf. Corresponds to Dosing Day 30 for Cycle 2 and dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

30. Steady-state Volume (Vss) of Total Calicheamicin (Conjugated Plus Unconjugated) Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Vss: Steady-state volume of distribution CL*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

31. Mean Residence Time (MRT) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    MRT: AUMCinf/AUCinf - DOF/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

32. Serum Decay Half-Life (t1/2) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

33. Area Under the Steady-state Serum Concentration-time Curve (AUClast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

34. Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

35. Peak Serum Concentration (Cmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

36. Time of Observed Maximum Concentration (Tmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin + Rituximab on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

37. Minimum Observed Serum Trough Concentration (Cmin) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin+Rituximab on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

38. Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

39. Area Under the Steady-state Concentration-time Curve (AUClast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

40. Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

41. Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

42. Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD+ Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

43. Peak Concentration (Cmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

44. Time to Reach Maximum Concentration (Tmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 [Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.

45. Average Serum Concentration (Cav) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

46. Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

47. Clearance (CL) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Clearance defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

48. Steady-state Volume (Vss) of Inotuzumab Ozogamicin Antibody Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 [Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85]

    Vss: Steady-state volume of distribution CL*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with CD20 and CD22-positive, follicular or diffuse large B-cell NHL who have not responded or progressed after 1 or 2 prior therapies; or subjects with CD20 and CD22-positive intermediate/aggressive NHL (diffuse large B-cell, mantle cell, transformed follicular or follicular grade 3b NHL) who have not responded or progressed after 1 or more prior therapies and are refractory to a previous rituximab containing therapy.

• Prior therapy must contain at least one course of rituximab therapy, as single agent or in combination.

• Measurable disease.

Exclusion Criteria:

• Subjects who are candidates for other potentially curative therapies.

• Subjects must not have received previous radioimmunotherapy.

• Subjects who have undergone a prior bone marrow transplantation within the last 6 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham-	Birmingham	Alabama	United States	35249 - 3300
2	IDS Pharmacy	Birmingham	Alabama	United States	35249
3	University of Alabama at Birmingham-	Birmingham	Alabama	United States	35294
4	California Cancer Care, Inc.	Greenbrae	California	United States	94904
5	University of California Medical Center	San Francisco	California	United States	94143
6	California Cancer Care	San Mateo	California	United States	94402
7	Emory Clinic	Atlanta	Georgia	United States	30322
8	Emory University Hospital	Atlanta	Georgia	United States	30322
9	Emory University Investigational Drug Service	Atlanta	Georgia	United States	30322
10	Northwestern Medical Faculty Foundation	Chicago	Illinois	United States	60611
11	Nevada Cancer Institute-	Las Vegas	Nevada	United States	89135
12	Rosewell Park Cancer Institute	Buffalo	New York	United States	14263
13	Gabrail Cancer Center	Canton	Ohio	United States	44718
14	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
15	Cleveland Clinic	Cleveland	Ohio	United States	44195
16	Gabrail Cancer Center	Dover	Ohio	United States	44622
17	UHHS - Westlake	Westlake	Ohio	United States	44145
18	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
19	The University of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030-4009
20	Royal Brisbane and Women's Hospital	Herston	Brisbane, QLD	Australia	4029
21	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven	Vlaams-brabant	Belgium	3000
22	Universitair Ziekenhuis Gent	Gent		Belgium	9000
23	University Hospital Gent - Department of Hematology	Gent		Belgium	9000
24	Hôpital André MIGNOT	Le Chesnay		France	78157
25	Hôpital Saint-Louis	Paris		France	75010
26	CH Lyon Sud	Pierre Benite		France	69495
27	Universitaetsklinik Bonn, Medizinische Klinik und Poliklinik III	Bonn		Germany	53105
28	Universitaetsmedizin der Johannes Gutenberg-Universitaet, III. medizinische klinik und Poliklinik	Mainz		Germany	55131
29	Prince Of Wales Hospital	Shatin N.T.		Hong Kong
30	Universita La Sapienza Cattedra di Ematologia	Roma		Italy	00161
31	Asan Medical Center	Seoul		Korea, Republic of	138-736
32	Erasmus Medisch Centrum--	Rotterdam	Zuid-holland	Netherlands	3015 CE
33	Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie	Warszawa		Poland	02-781
34	Hospital Clinic I Provincial de Barcelona	Barcelona		Spain	08028
35	University Hospital Zurich	Zurich		Switzerland	8091
36	Derriford Hospital - Plymouth	Plymouth	Devon	United Kingdom	PL6 8DH
37	Somers Cancer Science Building MP824	Southampton	Hampshire	United Kingdom	SO16 6YD
38	Bart's Cancer Institute; Queen Mary University of London	London		United Kingdom	EC1M 6BQ

Sponsors and Collaborators

• Pfizer
• UCB Pharma

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00299494
• Other Study ID Numbers: 3129K3-101; B1931004; 2005-005436-27
• First Posted: Mar 6, 2006
• Last Update Posted: Mar 8, 2018
• Last Verified: Feb 1, 2018

• Keywords provided by Pfizer: Lymphoma; NHL
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Rituximab; Inotuzumab Ozogamicin

Study Results

Participant Flow

Recruitment Details	A Open-Label, Phase 1/2 Study of CMC-544 (Inotuzumab Ozogamicin) in Combination With Rituximab in Subjects
Pre-assignment Detail	Eligible Subjects were Randomly Assigned to Study Treatments

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via intravenous (IV) infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the maximum tolerated dose (MTD) determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with diffuse large B-cell lymphoma (DLBCL) received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with either refractory aggressive or intermediate B-cell non-Hodgkin's lymphoma (NHL) received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Period Title: Overall Study
STARTED	5	3	7	34	40	30
COMPLETED	2	2	3	24	13	4
NOT COMPLETED	3	1	4	10	27	26

Baseline Characteristics

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)	Total
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Total of all reporting groups
Overall Participants	5	3	7	34	40	30	119
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.4 (10.9)	65.7 (0.6)	60.7 (9.6)	61.7 (12.2)	67.2 (13.0)	55.5 (15.8)	62.1 (13.7)
Sex: Female, Male (Count of Participants)
Female	2 40%	1 33.3%	1 14.3%	18 52.9%	17 42.5%	9 30%	48 40.3%
Male	3 60%	2 66.7%	6 85.7%	16 47.1%	23 57.5%	21 70%	71 59.7%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin in Combination With Rituximab (375 mg/m^2 )
Description	Inotuzumab ozogamicin was dose escalated (3 to 6 evaluable participants enrolled per dose cohort) during the first 28 days after the first administration of inotuzumab ozogamicin + rituximab. Enrollment at the next dose level or enrollment of additional subjects into a cohort proceeded according to the following criteria: 0 dose-limiting toxicity (DLT) by Day 28 of first dose move to higher dose, 1 participant reporting DLT but no others in cohort by Day 28 of first dose move to higher dose, greater than 2 participants reporting DLT by Day 28 of first dose stop and prior dose level considered MTD. The worldwide medical monitor and investigators reviewed all significant study drug-related toxicities to determine if the dose escalation rules were satisfied and whether the dose escalation schedule required modification.
Time Frame	First 28-day cycle

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) Population: All participants included in the intended dose scheme. One additional participant was enrolled over the 6 planned participants in 1.8 mg/m^2 dose cohort because 1 participant was unevaluable for MTD evaluations.

Arm/Group Title	INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin (0.8 mg/m^2, 1.3 mg/m^2, or 1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	15
Number [mg/m^2]	1.8

2. Primary Outcome

Title	Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population)
Description	A TEAE is any event that occurred after the first dose of study drug up to 56 days post the last dose of study drug (either rituximab or inotuzumab ozogamicin).
Time Frame	Protocol reporting period of from informed consent to at least 28 days after the last dose. This outcome measure time frame: From the first dose of study drug to up to 56 days after the last dose of either study drug.

Outcome Measure Data

Analysis Population Description

Safety population: All participants receiving at least 1 dose of inotuzumab ozogamicin or rituximab.

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	5	3	7	34	40	30
% participants with a TEAE	100 2000%	100 3333.3%	100 1428.6%	100 294.1%	100 250%	100 333.3%
% participants with serious TEAE	20.0 400%	0 0%	14.3 204.3%	26.5 77.9%	30.0 75%	16.7 55.7%
% participants with Grade 3 or 4 TEAE	80.0 1600%	66.7 2223.3%	71.4 1020%	67.6 198.8%	75.0 187.5%	63.3 211%
% participants with Grade 5 TEAE	20.0 400%	0 0%	0 0%	0 0%	2.5 6.3%	6.7 22.3%
% participants for study drug discontinuation	0 0%	33.3 1110%	28.6 408.6%	61.8 181.8%	50.0 125%	33.3 111%
% participants with dose reduction due to TEAE	0 0%	0 0%	14.3 204.3%	14.7 43.2%	10.0 25%	0 0%
% participants for study drug stopped temporarily	20.0 400%	0 0%	42.9 612.9%	44.1 129.7%	40.0 100%	10.0 33.3%

3. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR)
Description	CR: a. Complete disappearance of all detectable clinical and radiographic evidence of disease, disease-related symptoms, and normalization of NHL assignable biochemical abnormalities ; b. lymph nodes and nodal masses must have regressed to normal size; c. Spleen regressed in size and not palpable on physical exam, size of other organs enlarged due to disease decreased in size; d. Repeat bone marrow infiltrate clear. CRu: CR but allows for a. Residual lymph node mass >1.5 cm in greatest transverse diameter has regressed by more than 75% in diameter. Individual nodes that were previously confluent regressed more than 75 % in their product diameters; b. Indeterminate bone marrow. PR: a. ≥50 % decrease in product of the diameters (SPD) of the 6 largest dominant nodes or nodal masses; b. No increase in size of other nodes, liver, or spleen, c. Liver or spleen nodules regressed ≥50% in the SPD; d. Other organs usually assessable, no measurable disease present.
Time Frame	Approximately every 2 (during treatment) or 3 (during follow-up) to 6 months for up to 5 years from 1st dose

Outcome Measure Data

Analysis Population Description

ITT population: all participants enrolled into the intended dose scheme. Using exact method based on binomial distribution.

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	5	3	7	34	40	30
Number (95% Confidence Interval) [Percentage of participants]	40 800%	100 3333.3%	57.1 815.7%	94.1 276.8%	72.5 181.3%	20 66.7%

4. Secondary Outcome

Title	Kaplan-Meier Estimates of Progression Free Survival (PFS)
Description	The Kaplan-Meier method was used to determine PFS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by >= 50% in the size of previously involved sites, c. >= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. >= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver.
Time Frame	From the date of first dose of test article until the first date on which disease progression or death was documented or new anticancer start, any of which could be reported up to 5 years post last dose

Outcome Measure Data

Analysis Population Description

ITT population. Calculated using Kaplan-Meier method.

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	5	3	7	34	40	30
Median (95% Confidence Interval) [Months]	1.7	NA	NA	NA	17.1	1.8

5. Secondary Outcome

Title	Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months
Description	Progression Free Survival is defined as the time interval from the first dose of test article until the first date on which relapsed disease, progression, initiation of new anti-cancer treatment due to persistent/refractory disease, or death was documented, censored at the last tumor evaluation.
Time Frame	From the first dose to 6 months after first dose

Outcome Measure Data

Analysis Population Description

ITT population; Calculated using Kaplan-Meier method.

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	5	3	7	34	40	30
Number (95% Confidence Interval) [Probability]	0.4	1.0	0.6	1.0	0.7	0.2

6. Secondary Outcome

Title	Kaplan-Meier Estimates of Overall Survival (OS)
Description	OS was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
Time Frame	From the first dose up to 5 years post last dose

Outcome Measure Data

Analysis Population Description

ITT population. Calculated using Kaplan-Meier method.

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	5	3	7	34	40	30
Median (95% Confidence Interval) [Months]	7.4	NA	16.9	NA	58.3	8.4

7. Secondary Outcome

Title	Kaplan-Meier Estimates of the Probability of Survival at 6 Months
Description	Overall Survival (OS) was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
Time Frame	From the first dose to 6 months after first dose.

Outcome Measure Data

Analysis Population Description

ITT population. Calculated using Kaplan-Meier method.

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	5	3	7	34	40	30
Number (95% Confidence Interval) [Probability]	0.6	1.0	0.7	1.0	0.9	0.6

8. Secondary Outcome

Title	Kaplan-Meier Estimates of Time to Tumor Progression (TTP)
Description	TTP is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by >= 50% in the size of previously involved sites, c. >= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. >= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determine TTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
Time Frame	From the date of first dose of test article until the first date on which disease progression or death was documented, any of which could be reported up to 5 years post last dose.

Outcome Measure Data

Analysis Population Description

ITT population. Calculated using Kaplan-Meier method.

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	5	3	7	34	40	30
Median (95% Confidence Interval) [Months]	1.7	NA	NA	NA	45.1	1.7

9. Secondary Outcome

Title	Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months
Description	Time-to-Tumor Progression (TTP): is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by >=50% in the size of previously involved sites, c. >= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. >= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determineTTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
Time Frame	From enrollment to up to 6 months from 1st dose.

Outcome Measure Data

Analysis Population Description

ITT population. Calculated using Kaplan-Meier method.

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	5	3	7	34	40	30
Number (95% Confidence Interval) [Probability]	0.4	1.0	0.7	1.0	0.7	0.3

10. Secondary Outcome

Title	Duration of Response (CR+CRu+PR)
Description	Time from date measurement criteria met for CR, CRu, or PR (whichever occurred first) until first date relapsed disease/date of death. CR: Complete disappearance of all detectable clinical, radiographic evidence of disease, disease-related symptoms, normalization of NHL assignable biochemical abnormalities; lymph nodes, nodal masses regressed to normal size; spleen size regressed, not palpable on physical exam, size of other organs enlarged due to disease. CRu: CR but allows for: residual lymph node mass >1.5 cm in greatest transverse diameter that regressed >75% in product diameter. Individual nodes previously confluent, regressed by >75% in their product diameters; Indeterminate bone marrow. PR: ≥50% decrease in SPD of 6 largest dominant nodes/nodal masses; No increase in size of other nodes, liver, or spleen; Splenic/hepatic nodules regressed by ≥50% in SPD; Except splenic/hepatic nodules, involvement of other organs assessable and no measurable disease present.
Time Frame	Time from date measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the first date relapsed disease or date of death (whichever occurs first) is objectively documented.

Outcome Measure Data

Analysis Population Description

ITT population. Calculated using Kaplan-Meier method using the number of participants that responded.

Arm/Group Title	INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL)	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY)
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	5	3	7	34	40	30
Median (95% Confidence Interval) [Month]	NA	NA	NA	NA	43.2	3.9

11. Secondary Outcome

Title	Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Serum concentration of inotuzumab ozogamicin on Dosing Days 30 and 58 were measured. AUCinf of inotuzumab ozogamicin was reported. AUCinf: AUClast (area under the serum concentration-time profile for inotuzumab ozogamicin from time zero to the time of the last quantifiable concentration) +(Clast [last quantifiable concentration]/kel [elimination rate constant]) where Clast is the predicted serum concentration of inotuzumab ozogamicin at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	36030 (34)
Dosing Day 58	40550 (28)

12. Secondary Outcome

Title	AUClast of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUC of inotuzumab ozogamicin was reported. AUClast is area under the serum concentration-time profile from time zero to the time of the Clast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population: all participants dosed with inotuzumab ozogamicin.

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	6157 (190)
Dosing Day 30	9664 (76191)
Dosing Day 58	17320 (225)

13. Secondary Outcome

Title	Time of the Last Quantifiable Serum Concentration in a Dosing Interval (Tlast) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Tlast of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 was reported. Tlast: Time of last quantifiable concentration of inotuzumab ozogamicin. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	44.2
Dosing Day 30	53.9
Dosing Day 58	137

14. Secondary Outcome

Title	Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Steady-state serum concentrations of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUCtau of inotuzumab ozogamicin was reported. AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	18660 (36)
Dosing Day 30	35900 (28)
Dosing Day 58	38820 (30)

15. Secondary Outcome

Title	Peak Serum Concentration (Cmax) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 were measured. Cmax of inotuzumab ozogamicin was reported. Cmax was observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	600.2 (42)
Dosing Day 30	378.3 (6435)
Dosing Day 58	519.2 (586)

16. Secondary Outcome

Title	Time to Reach Maximum Concentration (Tmax) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	1.00
Dosing Day 30	1.08
Dosing Day 58	1.08

17. Secondary Outcome

Title	Average Serum Concentration at Steady State (Cav) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Cav: AUCtau (Area under the concentration time profile)/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	53.43 (28)
Dosing Day 58	57.77 (30)

18. Secondary Outcome

Title	Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58
Description	Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	0.0001196 (384)
Dosing Day 58	0 (0)

19. Secondary Outcome

Title	Clearance (CL) of Serum Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58
Description	Clearance is defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Cycle 2 Day 30	0.09855 (33)
Cycle 3 Day 58	0.08743 (37)

20. Secondary Outcome

Title	Steady-state Volume of Distribution (Vss) of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab MTD+Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Vss of inotuzumab ozogamicin on Dosing Days 30 and 58 were reported. Vss=CL*MRT (mean residence time). Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	4.860 (37)
Dosing Day 58	5.183 (38)

21. Secondary Outcome

Title	MRT of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	MRT: AUMCinf/AUCinf - DOF (degrees of freedom)/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	49.31 (39)
Dosing Day 58	59.24 (27)

22. Secondary Outcome

Title	Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	40.15
Dosing Day 58	43.00

23. Secondary Outcome

Title	AUCinf of Total Calicheamicin (Conjugated + Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	8437 (39)
Dosing Day 58	10060 (58)

24. Secondary Outcome

Title	AUClast of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	1901 (192)
Dosing Day 30	6129 (85)
Dosing Day 58	6755 (145)

25. Secondary Outcome

Title	Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	149
Dosing Day 30	312
Dosing Day 58	458

26. Secondary Outcome

Title	Area Under the Steady-state Serum Concentration-time Curve (AUCtau) for Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58
Description	AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	3201 (78)
Dosing Day 30	7794 (38)
Dosing Day 58	9197 (54)

27. Secondary Outcome

Title	Peak Serum Concentration (Cmax) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	54.36 (226)
Dosing Day 30	58.67 (283)
Dosing Day 58	64.43 (47)

28. Secondary Outcome

Title	Time of Observed Maximum Concentration (Tmax) of Total Calicheamicin (Conjugated+Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	1.05
Dosing Day 30	1.26
Dosing Day 58	1.38

29. Secondary Outcome

Title	Average Serum Concentration (Cav) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	11.60 (38)
Dosing Day 58	13.69 (54)

30. Secondary Outcome

Title	Minimum Observed Serum Trough Concentration (Cmin) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	0.0001326 (564)
Dosing Day 58	0.0001350 (497)

31. Secondary Outcome

Title	Clearance (CL) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Clearance defined as Dose/AUCinf. Corresponds to Dosing Day 30 for Cycle 2 and dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	0.4353 (40)
Dosing Day 58	0.3799 (57)

32. Secondary Outcome

Title	Steady-state Volume (Vss) of Total Calicheamicin (Conjugated Plus Unconjugated) Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Vss: Steady-state volume of distribution CL*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	72.95 (35)
Dosing Day 58	75.81 (26)

33. Secondary Outcome

Title	Mean Residence Time (MRT) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	MRT: AUMCinf/AUCinf - DOF/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	167.5 (41)
Dosing Day 58	199.5 (49)

34. Secondary Outcome

Title	Serum Decay Half-Life (t1/2) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

Pk population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 30	126.5
Dosing Day 58	176.0

35. Secondary Outcome

Title	Area Under the Steady-state Serum Concentration-time Curve (AUClast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	0.0009904 (22500000)
Dosing Day 30	0.002008 (64300000)
Dosing Day 58	0.005896 (1370000000)

36. Secondary Outcome

Title	Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 1	48.5
Dosing Day 30	4.00
Dosing Day 58	4.00

37. Secondary Outcome

Title	Peak Serum Concentration (Cmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
Measure Participants	104
Dosing Day 1	0.0005608 (121496)
Dosing Day 30	0.001153 (1020000)
Dosing Day 58	0.003250 (6780000)

38. Secondary Outcome

Title	Time of Observed Maximum Concentration (Tmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin + Rituximab on Dosing Day 1, Day 30 and Day 58
Description	Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 1	1.38
Dosing Day 30	4.00
Dosing Day 58	3.42

39. Secondary Outcome

Title	Minimum Observed Serum Trough Concentration (Cmin) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin+Rituximab on Dosing Day 30 and Day 58
Description	Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 30	0.0001588 (1044)
Dosing Day 58	0.0001495 (811)

40. Secondary Outcome

Title	Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m2 on Dosing Day 30 and Day 58
Description	AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 30	83270 (36)
Dosing Day 58	93760 (30)

41. Secondary Outcome

Title	Area Under the Steady-state Concentration-time Curve (AUClast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 1	25740 (139)
Dosing Day 30	61770 (88)
Dosing Day 58	72430 (95)

42. Secondary Outcome

Title	Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 1	190
Dosing Day 30	310
Dosing Day 58	312

43. Secondary Outcome

Title	Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab on Dosing Day 30 and Day 58
Description	Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 30	99.35
Dosing Day 58	103.5

44. Secondary Outcome

Title	Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD+ Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58
Description	AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 1	40180 (51)
Dosing Day 30	80060 (37)
Dosing Day 58	91370 (32)

45. Secondary Outcome

Title	Peak Concentration (Cmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 1	776.6 (36)
Dosing Day 30	700.4 (448)
Dosing Day 58	653.0 (625)

46. Secondary Outcome

Title	Time to Reach Maximum Concentration (Tmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Description	Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 1	1.05
Dosing Day 30	1.17
Dosing Day 58	3.79

47. Secondary Outcome

Title	Average Serum Concentration (Cav) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 30	119.2 (37)
Dosing Day 58	136 (32)

48. Secondary Outcome

Title	Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 30	0.0001190 (366)
Dosing Day 58	0 (0)

49. Secondary Outcome

Title	Clearance (CL) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Clearance defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK populatoin

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the first cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 30	0.04240 (41)
Dosing Day 58	0.03699 (36)

50. Secondary Outcome

Title	Steady-state Volume (Vss) of Inotuzumab Ozogamicin Antibody Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Description	Vss: Steady-state volume of distribution CL*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time Frame	Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2
Arm/Group Description	Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma, DLBCL, and refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment.
Measure Participants	104
Dosing Day 30	5.283 (29)
Dosing Day 58	4.952 (34)

Adverse Events

Time Frame	Adverse events were recorded and reported from the time a participant signed the Informed Consent Form (ICF) until at least 28 days after last dose of study treatment. Summarized data reflects incidents from 1st dose to up to 56 days post last dose.
Adverse Event Reporting Description	The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Inotuzumab Ozogamicin 0.8 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin 1.3 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin 1.8 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 Follicular		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 DLBCL		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 Refractory
Arm/Group Description	Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.		Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.		Participants received rituximab 375 mg/m^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.		Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.		Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.		Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the subject refused further treatment.
All Cause Mortality
	Inotuzumab Ozogamicin 0.8 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin 1.3 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin 1.8 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 Follicular		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 DLBCL		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 Refractory
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Inotuzumab Ozogamicin 0.8 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin 1.3 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin 1.8 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 Follicular		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 DLBCL		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 Refractory
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		0/3 (0%)		1/7 (14.3%)		9/34 (26.5%)		12/40 (30%)		5/30 (16.7%)
Blood and lymphatic system disorders
Neutropenia	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Thrombocytopenia	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		1/40 (2.5%)		0/30 (0%)
Cardiac disorders
Atrial fibrillation	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Bundle branch block left	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Cardiac arrest	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Cardiac failure congestive	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Gastrointestinal disorders
Barrett's oesophagus	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Constipation	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Duodenal ulcer	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Duodenitis	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Gastrointestinal perforation	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Intestinal ischaemia	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Nausea	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		2/40 (5%)		0/30 (0%)
Oesophagitis	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Upper gastrointestinal haemorrhage	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Visceroptosis	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Vomiting	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		2/40 (5%)		0/30 (0%)
General disorders
Chest pain	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Chills	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Disease progression	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		1/30 (3.3%)
Fatigue	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
General physical health deterioration	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Local swelling	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Malaise	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Oedema peripheral	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Pain	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Pyrexia	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Hepatobiliary disorders
Hepatocellular injury	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Infections and infestations
Bronchitis	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Candida pneumonia	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Clostridium difficile colitis	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Escherichia bacteraemia	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Herpes zoster	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Infection	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Intervertebral discitis	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Pneumonia	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		1/40 (2.5%)		0/30 (0%)
Pneumonia klebsiella	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Sepsis	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		1/30 (3.3%)
Staphylococcal bacteraemia	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Musculoskeletal and connective tissue disorders
Neck pain	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Pain in extremity	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Non-Hodgkin's lymphoma	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Nervous system disorders
Convulsion	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Dizziness	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		2/40 (5%)		0/30 (0%)
Somnolence	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Syncope	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Psychiatric disorders
Delirium	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Dyspnoea	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Pneumothorax spontaneous	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Skin and subcutaneous tissue disorders
Spider naevus	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Vascular disorders
Haemorrhage	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Shock	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Other (Not Including Serious) Adverse Events
	Inotuzumab Ozogamicin 0.8 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin 1.3 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin 1.8 mg/m^2+ Rituximab 375 mg/m^2		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 Follicular		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 DLBCL		Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 Refractory
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		3/3 (100%)		7/7 (100%)		34/34 (100%)		39/40 (97.5%)		30/30 (100%)
Blood and lymphatic system disorders
Anaemia	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		3/34 (8.8%)		7/40 (17.5%)		3/30 (10%)
Hyperfibrinogenaemia	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Leukopenia	2/5 (40%)		0/3 (0%)		1/7 (14.3%)		5/34 (14.7%)		5/40 (12.5%)		4/30 (13.3%)
Lymphopenia	1/5 (20%)		0/3 (0%)		1/7 (14.3%)		1/34 (2.9%)		9/40 (22.5%)		1/30 (3.3%)
Neutropenia	2/5 (40%)		0/3 (0%)		4/7 (57.1%)		18/34 (52.9%)		11/40 (27.5%)		4/30 (13.3%)
Thrombocytopenia	2/5 (40%)		2/3 (66.7%)		5/7 (71.4%)		15/34 (44.1%)		27/40 (67.5%)		16/30 (53.3%)
Cardiac disorders
Angina pectoris	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Eye disorders
Eye irritation	0/5 (0%)		0/3 (0%)		0/7 (0%)		4/34 (11.8%)		5/40 (12.5%)		1/30 (3.3%)
Eye pain	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Lacrimation increased	0/5 (0%)		0/3 (0%)		0/7 (0%)		4/34 (11.8%)		1/40 (2.5%)		0/30 (0%)
Ocular hyperaemia	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		0/40 (0%)		0/30 (0%)
Periorbital oedema	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		0/40 (0%)		0/30 (0%)
Vision blurred	0/5 (0%)		0/3 (0%)		0/7 (0%)		4/34 (11.8%)		2/40 (5%)		0/30 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		1/40 (2.5%)		0/30 (0%)
Abdominal distension	0/5 (0%)		0/3 (0%)		0/7 (0%)		3/34 (8.8%)		0/40 (0%)		1/30 (3.3%)
Abdominal pain	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		6/34 (17.6%)		4/40 (10%)		4/30 (13.3%)
Abdominal pain upper	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		3/34 (8.8%)		1/40 (2.5%)		2/30 (6.7%)
Abdominal tenderness	1/5 (20%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		1/40 (2.5%)		0/30 (0%)
Ascites	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		3/30 (10%)
Constipation	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		9/34 (26.5%)		13/40 (32.5%)		5/30 (16.7%)
Diarrhoea	0/5 (0%)		1/3 (33.3%)		1/7 (14.3%)		9/34 (26.5%)		8/40 (20%)		9/30 (30%)
Dry mouth	0/5 (0%)		0/3 (0%)		0/7 (0%)		5/34 (14.7%)		1/40 (2.5%)		1/30 (3.3%)
Dyspepsia	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		3/34 (8.8%)		3/40 (7.5%)		2/30 (6.7%)
Dysphagia	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Gingival bleeding	1/5 (20%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Gingival pain	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		1/40 (2.5%)		0/30 (0%)
Haematemesis	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Hyperchlorhydria	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Melaena	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Nausea	0/5 (0%)		0/3 (0%)		5/7 (71.4%)		24/34 (70.6%)		24/40 (60%)		11/30 (36.7%)
Odynophagia	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Oral pain	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		2/40 (5%)		0/30 (0%)
Stomatitis	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		2/40 (5%)		0/30 (0%)
Tongue disorder	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Toothache	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		1/40 (2.5%)		1/30 (3.3%)
Vomiting	1/5 (20%)		0/3 (0%)		3/7 (42.9%)		13/34 (38.2%)		8/40 (20%)		7/30 (23.3%)
General disorders
Asthenia	1/5 (20%)		0/3 (0%)		1/7 (14.3%)		2/34 (5.9%)		4/40 (10%)		1/30 (3.3%)
Catheter site erythema	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Catheter site pruritus	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Chest discomfort	0/5 (0%)		0/3 (0%)		2/7 (28.6%)		1/34 (2.9%)		2/40 (5%)		1/30 (3.3%)
Chest pain	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Chills	1/5 (20%)		1/3 (33.3%)		2/7 (28.6%)		4/34 (11.8%)		12/40 (30%)		2/30 (6.7%)
Crepitations	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Fatigue	5/5 (100%)		1/3 (33.3%)		5/7 (71.4%)		16/34 (47.1%)		22/40 (55%)		13/30 (43.3%)
Influenza like illness	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		4/34 (11.8%)		0/40 (0%)		1/30 (3.3%)
Local swelling	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		2/40 (5%)		0/30 (0%)
Malaise	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Oedema	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		2/40 (5%)		0/30 (0%)
Oedema peripheral	1/5 (20%)		1/3 (33.3%)		1/7 (14.3%)		4/34 (11.8%)		7/40 (17.5%)		4/30 (13.3%)
Pain	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		1/34 (2.9%)		1/40 (2.5%)		2/30 (6.7%)
Pyrexia	0/5 (0%)		1/3 (33.3%)		4/7 (57.1%)		12/34 (35.3%)		8/40 (20%)		7/30 (23.3%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/5 (0%)		0/3 (0%)		0/7 (0%)		12/34 (35.3%)		13/40 (32.5%)		9/30 (30%)
Immune system disorders
Cytokine release syndrome	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Infections and infestations
Bronchitis	1/5 (20%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Catheter site infection	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Conjunctivitis	1/5 (20%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		1/40 (2.5%)		2/30 (6.7%)
Nasopharyngitis	0/5 (0%)		0/3 (0%)		2/7 (28.6%)		2/34 (5.9%)		2/40 (5%)		0/30 (0%)
Oral candidiasis	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		0/40 (0%)		2/30 (6.7%)
Oropharyngitis fungal	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Rhinitis	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		3/34 (8.8%)		3/40 (7.5%)		1/30 (3.3%)
Sinusitis	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		0/40 (0%)		1/30 (3.3%)
Upper respiratory tract infection	1/5 (20%)		1/3 (33.3%)		1/7 (14.3%)		5/34 (14.7%)		2/40 (5%)		1/30 (3.3%)
Urinary tract infection	0/5 (0%)		0/3 (0%)		0/7 (0%)		4/34 (11.8%)		5/40 (12.5%)		1/30 (3.3%)
Injury, poisoning and procedural complications
Alcohol poisoning	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Fall	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Infusion related reaction	1/5 (20%)		0/3 (0%)		1/7 (14.3%)		3/34 (8.8%)		5/40 (12.5%)		2/30 (6.7%)
Investigations
Alanine aminotransferase increased	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		9/34 (26.5%)		11/40 (27.5%)		9/30 (30%)
Aspartate aminotransferase increased	2/5 (40%)		0/3 (0%)		3/7 (42.9%)		17/34 (50%)		18/40 (45%)		10/30 (33.3%)
Blood alkaline phosphatase increased	1/5 (20%)		0/3 (0%)		2/7 (28.6%)		15/34 (44.1%)		13/40 (32.5%)		7/30 (23.3%)
Blood bilirubin decreased	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		2/30 (6.7%)
Blood cholesterol increased	1/5 (20%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Blood creatine phosphokinase increased	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		2/30 (6.7%)
Blood creatinine increased	1/5 (20%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		2/40 (5%)		3/30 (10%)
Blood fibrinogen increased	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Blood glucose increased	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Blood lactate dehydrogenase increased	0/5 (0%)		0/3 (0%)		2/7 (28.6%)		9/34 (26.5%)		13/40 (32.5%)		6/30 (20%)
Blood triglycerides increased	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Blood urea increased	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		3/40 (7.5%)		1/30 (3.3%)
Blood urine present	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Body temperature increased	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		3/30 (10%)
Fibrin D dimer increased	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Gamma-glutamyltransferase increased	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		1/34 (2.9%)		4/40 (10%)		3/30 (10%)
Monocyte count increased	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		2/30 (6.7%)
Protein total increased	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		2/30 (6.7%)
Urine protein/creatinine ratio increased	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		3/40 (7.5%)		0/30 (0%)
Weight decreased	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		3/34 (8.8%)		6/40 (15%)		5/30 (16.7%)
White blood cell count increased	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		2/30 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	1/5 (20%)		0/3 (0%)		2/7 (28.6%)		9/34 (26.5%)		6/40 (15%)		6/30 (20%)
Dehydration	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		1/40 (2.5%)		1/30 (3.3%)
Fluid retention	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Hypercalcaemia	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Hyperglycaemia	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		2/34 (5.9%)		7/40 (17.5%)		4/30 (13.3%)
Hyperuricaemia	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		1/40 (2.5%)		2/30 (6.7%)
Hypoalbuminaemia	0/5 (0%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		5/40 (12.5%)		0/30 (0%)
Hypocalcaemia	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		2/40 (5%)		1/30 (3.3%)
Hypokalaemia	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		5/34 (14.7%)		6/40 (15%)		3/30 (10%)
Hypomagnesaemia	0/5 (0%)		0/3 (0%)		0/7 (0%)		7/34 (20.6%)		2/40 (5%)		1/30 (3.3%)
Hypophagia	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		0/40 (0%)		0/30 (0%)
Hypophosphataemia	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		3/40 (7.5%)		3/30 (10%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)		0/3 (0%)		0/7 (0%)		5/34 (14.7%)		2/40 (5%)		1/30 (3.3%)
Back pain	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		4/34 (11.8%)		5/40 (12.5%)		2/30 (6.7%)
Bone pain	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		3/40 (7.5%)		0/30 (0%)
Groin pain	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		2/40 (5%)		0/30 (0%)
Muscle spasms	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		4/30 (13.3%)
Musculoskeletal pain	0/5 (0%)		0/3 (0%)		2/7 (28.6%)		1/34 (2.9%)		3/40 (7.5%)		2/30 (6.7%)
Myalgia	2/5 (40%)		0/3 (0%)		0/7 (0%)		6/34 (17.6%)		4/40 (10%)		0/30 (0%)
Neck pain	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		3/40 (7.5%)		1/30 (3.3%)
Pain in extremity	1/5 (20%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		2/40 (5%)		0/30 (0%)
Spinal pain	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		0/40 (0%)		0/30 (0%)
Tendonitis	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Nervous system disorders
Disturbance in attention	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Dizziness	1/5 (20%)		1/3 (33.3%)		0/7 (0%)		11/34 (32.4%)		6/40 (15%)		1/30 (3.3%)
Dysgeusia	0/5 (0%)		0/3 (0%)		0/7 (0%)		3/34 (8.8%)		1/40 (2.5%)		0/30 (0%)
Headache	0/5 (0%)		1/3 (33.3%)		3/7 (42.9%)		12/34 (35.3%)		5/40 (12.5%)		5/30 (16.7%)
Hypogeusia	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		0/40 (0%)		0/30 (0%)
Memory impairment	0/5 (0%)		0/3 (0%)		0/7 (0%)		7/34 (20.6%)		3/40 (7.5%)		0/30 (0%)
Migraine	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		1/40 (2.5%)		0/30 (0%)
Paraesthesia	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		2/34 (5.9%)		2/40 (5%)		0/30 (0%)
Syncope	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Tremor	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Psychiatric disorders
Anxiety	1/5 (20%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		2/40 (5%)		1/30 (3.3%)
Depression	0/5 (0%)		0/3 (0%)		0/7 (0%)		3/34 (8.8%)		1/40 (2.5%)		0/30 (0%)
Insomnia	0/5 (0%)		0/3 (0%)		0/7 (0%)		4/34 (11.8%)		4/40 (10%)		1/30 (3.3%)
Sleep disorder	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Renal and urinary disorders
Dysuria	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		2/34 (5.9%)		1/40 (2.5%)		2/30 (6.7%)
Urine odour abnormal	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Reproductive system and breast disorders
Gynaecomastia	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Nipple pain	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/5 (0%)		1/3 (33.3%)		3/7 (42.9%)		9/34 (26.5%)		5/40 (12.5%)		8/30 (26.7%)
Dysphonia	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		1/40 (2.5%)		0/30 (0%)
Dyspnoea	2/5 (40%)		0/3 (0%)		0/7 (0%)		9/34 (26.5%)		6/40 (15%)		5/30 (16.7%)
Dyspnoea exertional	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		0/40 (0%)		1/30 (3.3%)
Epistaxis	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		9/34 (26.5%)		8/40 (20%)		4/30 (13.3%)
Nasal congestion	0/5 (0%)		0/3 (0%)		0/7 (0%)		3/34 (8.8%)		0/40 (0%)		0/30 (0%)
Oropharyngeal pain	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		5/34 (14.7%)		1/40 (2.5%)		3/30 (10%)
Painful respiration	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Pleural effusion	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		1/40 (2.5%)		2/30 (6.7%)
Productive cough	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		2/40 (5%)		2/30 (6.7%)
Pulmonary oedema	1/5 (20%)		0/3 (0%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Rhinitis allergic	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Rhinorrhoea	0/5 (0%)		0/3 (0%)		0/7 (0%)		3/34 (8.8%)		1/40 (2.5%)		1/30 (3.3%)
Tonsillar hypertrophy	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Wheezing	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		1/30 (3.3%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Dry skin	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		1/34 (2.9%)		0/40 (0%)		0/30 (0%)
Ecchymosis	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		1/40 (2.5%)		1/30 (3.3%)
Erythema	0/5 (0%)		0/3 (0%)		0/7 (0%)		3/34 (8.8%)		1/40 (2.5%)		0/30 (0%)
Hyperhidrosis	0/5 (0%)		0/3 (0%)		0/7 (0%)		2/34 (5.9%)		1/40 (2.5%)		1/30 (3.3%)
Night sweats	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		4/34 (11.8%)		1/40 (2.5%)		4/30 (13.3%)
Pruritus	2/5 (40%)		1/3 (33.3%)		0/7 (0%)		2/34 (5.9%)		4/40 (10%)		1/30 (3.3%)
Rash	2/5 (40%)		1/3 (33.3%)		1/7 (14.3%)		6/34 (17.6%)		3/40 (7.5%)		0/30 (0%)
Rash pruritic	0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/34 (0%)		0/40 (0%)		0/30 (0%)
Vascular disorders
Flushing	1/5 (20%)		1/3 (33.3%)		0/7 (0%)		3/34 (8.8%)		3/40 (7.5%)		1/30 (3.3%)
Hot flush	1/5 (20%)		0/3 (0%)		0/7 (0%)		3/34 (8.8%)		0/40 (0%)		0/30 (0%)
Hypertension	0/5 (0%)		0/3 (0%)		0/7 (0%)		1/34 (2.9%)		3/40 (7.5%)		0/30 (0%)
Hypotension	0/5 (0%)		1/3 (33.3%)		1/7 (14.3%)		2/34 (5.9%)		1/40 (2.5%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.