Study Evaluating The Safety And Tolerability Of Combination Therapy Inotuzumab Ozogamicin (CMC-544) And Rituximab

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00724971
• Collaborator: (none)
• Enrollment: 10
• Locations: 4
• Arm: 1
• Actual Duration (Months): 20.2
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To assess the tolerability and the initial safety profile of Inotuzumab Ozogamicin (CMC-544) in combination with Rituximab in patients with B-Cell Non-Hodgkin's lymphoma (NHL).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, B-Cell	Drug: Inotuzumab Ozogamicin (CMC-544); Drug: Rituximab (Rituxan)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study Of Cmc-544 Administered In Combination With Rituximab In Subjects With B-cell Non-hodgkin's Lymphoma
• Actual Study Start Date: Jul 4, 2008
• Actual Primary Completion Date: Mar 10, 2010
• Actual Study Completion Date: Mar 10, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Inotuzumab Ozogamicin + Rituximab	Drug: Inotuzumab Ozogamicin (CMC-544); 1.8 mg/m2, IV on day 2 of each 28 day cycle; up to 8 cycles unless PD, unacceptable toxicity, or subject's refusal occurs.; Drug: Rituximab (Rituxan); 375 mg/m2, IV on day 1 of each 28 day cycle; up to 8 cycles unless PD, unacceptable toxicity, or subject's refusal occurs.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose-limiting Toxicities (DLT) [Up to 28 days]

   A DLT was defined as the following drug-related adverse event which occurred during the first 28 days: 1) Any National Cancer Institute (NCI) Grade 3 or 4 nonhematologic toxicity (except Grade 3 nausea or vomiting without optimal treatment), 2) Febrile neutropenia, 3) Grade 4 absolute neutrophil count lasting >=7 days, 4) Grade 4 thrombocytopenia lasting >=3 days, 5) Grade 3 or 4 thrombocytopenia associated with a bleeding episode requiring platelet transfusion, 6)Delayed recovery (to grade <=1 or baseline, except alopecia) from a drug-related toxicity that delayed the next dose >2 weeks

Secondary Outcome Measures

1. Number of Participants With Objective Response: Evaluable Population [Up to 8 cycles (1 cycle = 28 days)]

   Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or >75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or >=50% decrease in the SPD.

2. Number of Participants With Objective Response: Intent-to-treat (ITT) Population [Up to 8 cycles (1 cycle = 28 days)]

   Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or >75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or >=50% decrease in the SPD.

3. Progression-Free Survival (PFS) [Up to 591 days]

   The interval from the date of first administration of the test article until the first date on which relapsed disease, progressive disease (PD), or death was documented, censored at the last tumor evaluation date. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: Relapse/PD, appearance of any new lesion or increased by >=50% in the size.

Other Outcome Measures

1. Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) [Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544]

   CMC-544 is composed of G544, an anti-human CD22 antibody, linked to a potent cytotoxic antitumor antibiotic called calicheamicin. CD22 is expressed on the malignant cells of the majority of B-lymphocyte malignancies.

2. Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 [Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544]

   The time measured for the serum concentration to decrease by one half.

3. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 [Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544]

   AUClast= Area under the serum concentration versus time curve from time zero (pre-dose) to time of last measured concentration.

4. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 [Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544]

   AUC∞ = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

5. Clearance (CL) of CMC-544, Total Calicheamicin, and G544 [Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544]

   The rate at which a drug is metabolized or eliminated by normal biological processes.

6. Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 [Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544]

   The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

7. Number of Participants With Positive Serum Antibody to Inotuzumab Ozogamicin (CMC-544) [Up to 8 Cycles (1 cycle = 28 days)]

   Antibody responses to CMC-544

8. Number of Participants With Positive Serum Antibody to Rituximab [Up to 8 Cycles (1 cycle = 28 days)]

   Antibody responses to rituximab

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• CD20 and CD22-positive, B-cell NHL which has progressed after 1 or 2 prior therapies.

• Prior therapy must have contained at least one dose of Rituximab therapy. Patients can not be refractory to Rituximab (refractory = PD under treatment or within 6 month

• Eastern Cooperative Oncology Group (ECOG) performance status: 0/ 1.

• Patients must not have received previous radioimmunotherapy.

• Patients tolerant to Rituximab.

• Patients must not have received chemotherapy, cancer immunosuppressive therapy, growth factors (except erythropoietin), or investigational agents within 28 days before first dose of test article.

Exclusion Criteria:

• Candidate for potentially curative therapies

• Subjects must not have received previous radioimmunotherapy.

• Subjects with autologous hematopoietic stem cell transplant within the last 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nagoya Daini Red Cross Hospital	Aichi		Japan	466-8650
2	Tokai University Hospital	Kanagawa		Japan	259-1193
3	National Cancer Center Hospital	Tokyo		Japan	104-0045
4	Cancer Inst. Hp. of Japanese Foundation for Cancer Research	Tokyo		Japan	135-8550

Sponsors and Collaborators

• Pfizer

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: NCT00724971
• Other Study ID Numbers: 3129K3-1104; B1931005
• First Posted: Jul 30, 2008
• Last Update Posted: Mar 15, 2019
• Last Verified: Nov 1, 2018

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

Study Results

Participant Flow

Pre-assignment Detail	Six consecutive patients were enrolled as the first cohort. The dose and administration were considered to be reasonable if <=2 participants in the first cohort experienced a dose limiting toxicity (DLT), and an additional 4 subjects were to be enrolled as the expanded cohort for a total 10 participants.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Period Title: Overall Study
STARTED	10
COMPLETED	4
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.20 (10.96)
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose-limiting Toxicities (DLT)
Description	A DLT was defined as the following drug-related adverse event which occurred during the first 28 days: 1) Any National Cancer Institute (NCI) Grade 3 or 4 nonhematologic toxicity (except Grade 3 nausea or vomiting without optimal treatment), 2) Febrile neutropenia, 3) Grade 4 absolute neutrophil count lasting >=7 days, 4) Grade 4 thrombocytopenia lasting >=3 days, 5) Grade 3 or 4 thrombocytopenia associated with a bleeding episode requiring platelet transfusion, 6)Delayed recovery (to grade <=1 or baseline, except alopecia) from a drug-related toxicity that delayed the next dose >2 weeks
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

The first cohort was analyzed for DLT.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	6
Count of Participants [Participants]	2 20%

2. Secondary Outcome

Title	Number of Participants With Objective Response: Evaluable Population
Description	Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or >75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or >=50% decrease in the SPD.
Time Frame	Up to 8 cycles (1 cycle = 28 days)

Outcome Measure Data

Analysis Population Description

The evaluable population included all participants who received at least 2 doses of the test article and who had a baseline tumor CT scan and underwent at least 1 postbaseline tumor assessment for anticancer clinical activity.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	8
Complete response (CR)	6 60%
Complete response unconfirmed (CRu)	1 10%
Partial response (PR)	0 0%
Objective Response (CR+CRu+PR)	7 70%

3. Secondary Outcome

Title	Number of Participants With Objective Response: Intent-to-treat (ITT) Population
Description	Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or >75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or >=50% decrease in the SPD.
Time Frame	Up to 8 cycles (1 cycle = 28 days)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were enrolled in the intended dose scheme.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	10
Complete response (CR)	6 60%
Complete response unconfirmed (CRu)	1 10%
Partial response (PR)	1 10%
Objective Response (CR+CRu+PR)	8 80%

4. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	The interval from the date of first administration of the test article until the first date on which relapsed disease, progressive disease (PD), or death was documented, censored at the last tumor evaluation date. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: Relapse/PD, appearance of any new lesion or increased by >=50% in the size.
Time Frame	Up to 591 days

Outcome Measure Data

Analysis Population Description

The evaluable population included all participants who received at least 2 doses of the test article and who had a baseline tumor computed tomography (CT) scan and underwent at least 1 postbaseline tumor assessment for anticancer clinical activity.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	8
Median (95% Confidence Interval) [weeks]	NA

5. Other Pre-specified Outcome

Title	Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544)
Description	CMC-544 is composed of G544, an anti-human CD22 antibody, linked to a potent cytotoxic antitumor antibiotic called calicheamicin. CD22 is expressed on the malignant cells of the majority of B-lymphocyte malignancies.
Time Frame	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544

Outcome Measure Data

Analysis Population Description

Phamacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	10
CMC-544: Cycle 1	559 (136)
CMC-544: Cycle 2	822 (152)
CMC-544: Cycle 3	958 (64.0)
Total Calicheamicin: Cycle 1	67.7 (14.9)
Total Calicheamicin: Cycle 2	80.2 (11.3)
Total Calicheamicin: Cycle 3	96.6 (2.89)
G544: Cycle 1	839 (157)
G544: Cycle 2	1110 (88.9)
G544: Cycle 3	1210 (177)

6. Other Pre-specified Outcome

Title	Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544
Description	The time measured for the serum concentration to decrease by one half.
Time Frame	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	10
CMC-544: Cycle 1	18.77 (1.09)
CMC-544: Cycle 2	29.08 (21.79)
CMC-544: Cycle 3	51.70 (20.59)
Total Calicheamicin: Cycle 1	61.23 (34.84)
Total Calicheamicin: Cycle 2	96.44 (31.31)
Total Calicheamicin: Cycle 3	167.87 (72.85)
G544: Cycle 1	67.14 (31.84)
G544: Cycle 2	101.59 (34.08)
G544: Cycle 3	127.57 (32.76)

7. Other Pre-specified Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544
Description	AUClast= Area under the serum concentration versus time curve from time zero (pre-dose) to time of last measured concentration.
Time Frame	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	10
CMC-544: Cycle 1	12300 (6200)
CMC-544: Cycle 2	27000 (7450)
CMC-544: Cycle 3	50100 (6390)
Total Calicheamicin: Cycle 1	2850 (1400)
Total Calicheamicin: Cycle 2	6490 (2250)
Total Calicheamicin: Cycle 3	10700 (4750)
G544: Cycle 1	38400 (16300)
G544: Cycle 2	84900 (23400)
G544: Cycle 3	127000 (44800)

8. Other Pre-specified Outcome

Title	Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544
Description	AUC∞ = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time Frame	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	10
CMC-544: Cycle 1	22300 (2850)
CMC-544: Cycle 2	34800 (12200)
CMC-544: Cycle 3	54800 (7070)
Total Calicheamicin: Cycle 1	4060 (1100)
Total Calicheamicin: Cycle 2	7460 (2540)
Total Calicheamicin: Cycle 3	12700 (5400)
G544: Cycle 1	47700 (14300)
G544: Cycle 2	92300 (26300)
G544: Cycle 3	138000 (42600)

9. Other Pre-specified Outcome

Title	Clearance (CL) of CMC-544, Total Calicheamicin, and G544
Description	The rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	10
CMC-544: Cycle 1	0.120 (0.0185)
CMC-544: Cycle 2	0.0782 (0.0192)
CMC-544: Cycle 3	0.0499 (0.0012)
Total Calicheamicin: Cycle 1	0.746 (0.212)
Total Calicheamicin: Cycle 2	0.424 (0.133)
Total Calicheamicin: Cycle 3	0.249 (0.0686)
G544: Cycle 1	0.0662 (0.0236)
G544: Cycle 2	0.0331 (0.0077)
G544: Cycle 3	0.0213 (0.0062)

10. Other Pre-specified Outcome

Title	Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544
Description	The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time Frame	Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	10
CMC-544: Cycle 1	2.33 (0.0763)
CMC-544: Cycle 2	2.26 (1.74)
CMC-544: Cycle 3	3.02 (1.23)
Total Calicheamicin: Cycle 1	47.6 (11.3)
Total Calicheamicin: Cycle 2	45.6 (7.04)
Total Calicheamicin: Cycle 3	47.8 (6.62)
G544: Cycle 1	3.95 (0.921)
G544: Cycle 2	3.39 (0.515)
G544: Cycle 3	3.02 (0.400)

11. Other Pre-specified Outcome

Title	Number of Participants With Positive Serum Antibody to Inotuzumab Ozogamicin (CMC-544)
Description	Antibody responses to CMC-544
Time Frame	Up to 8 Cycles (1 cycle = 28 days)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all participants in the intended dose scheme.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	10
Screening	1 10%
End of Treatment	0 0%

12. Other Pre-specified Outcome

Title	Number of Participants With Positive Serum Antibody to Rituximab
Description	Antibody responses to rituximab
Time Frame	Up to 8 Cycles (1 cycle = 28 days)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all participants in the intended dose scheme.

Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
Measure Participants	10
Screening	0 0%
End of Treatment	0 0%

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
Arm/Group Description	Participants were treated with intravenous rituximab (375 mg/m^2) followed by intravenous CMC-544 (1.8 mg/m^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least "stable disease (SD)" after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent.
All Cause Mortality
	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Anaemia	1/10 (10%)
Erythropenia	1/10 (10%)
Leukopenia	8/10 (80%)
Lymphocytosis	1/10 (10%)
Lymphopenia	6/10 (60%)
Monocytosis	1/10 (10%)
Neutropenia	7/10 (70%)
Thrombocytopenia	10/10 (100%)
Cardiac disorders
Arrhythmia	1/10 (10%)
Palpitations	1/10 (10%)
Ear and labyrinth disorders
Tinnitus	1/10 (10%)
Gastrointestinal disorders
Abdominal discomfort	1/10 (10%)
Abdominal distension	1/10 (10%)
Abdominal pain	1/10 (10%)
Abdominal pain upper	1/10 (10%)
Constipation	2/10 (20%)
Diarrhoea	1/10 (10%)
Epigastric discomfort	1/10 (10%)
Gastritis	1/10 (10%)
Glossitis	1/10 (10%)
Haemorrhoids	1/10 (10%)
Mouth haemorrhage	1/10 (10%)
Nausea	8/10 (80%)
Stomatitis	3/10 (30%)
Vomiting	1/10 (10%)
General disorders
Chills	2/10 (20%)
Extravasation	1/10 (10%)
Fatigue	5/10 (50%)
Influenza like illness	1/10 (10%)
Injection site reaction	1/10 (10%)
Malaise	2/10 (20%)
Pyrexia	3/10 (30%)
Hepatobiliary disorders
Hyperbilirubinaemia	4/10 (40%)
Immune system disorders
Cytokine release syndrome	1/10 (10%)
Food allergy	1/10 (10%)
Infections and infestations
Cystitis bacterial	1/10 (10%)
Nasopharyngitis	3/10 (30%)
Oral herpes	1/10 (10%)
Upper respiratory tract infection	1/10 (10%)
Injury, poisoning and procedural complications
Excoriation	1/10 (10%)
Mouth injury	1/10 (10%)
Investigations
Alanine aminotransferase increased	8/10 (80%)
Aspartate aminotransferase increased	9/10 (90%)
Blood alkaline phosphatase increased	5/10 (50%)
Blood amylase increased	1/10 (10%)
Blood calcium increased	1/10 (10%)
Blood glucose increased	2/10 (20%)
Blood lactate dehydrogenase increased	6/10 (60%)
Blood potassium decreased	1/10 (10%)
Blood sodium increased	1/10 (10%)
C-reactive protein increased	2/10 (20%)
Gamma-glutamyltransferase increased	3/10 (30%)
Glucose urine present	1/10 (10%)
Haematocrit decreased	1/10 (10%)
Haemoglobin decreased	3/10 (30%)
Protein total decreased	1/10 (10%)
Metabolism and nutrition disorders
Decreased appetite	5/10 (50%)
Hyperglycaemia	1/10 (10%)
Hypokalaemia	1/10 (10%)
Hypophosphataemia	2/10 (20%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/10 (10%)
Back pain	2/10 (20%)
Monarthritis	1/10 (10%)
Musculoskeletal pain	1/10 (10%)
Nervous system disorders
Dizziness	1/10 (10%)
Dysgeusia	1/10 (10%)
Headache	4/10 (40%)
Lethargy	1/10 (10%)
Psychiatric disorders
Insomnia	2/10 (20%)
Respiratory, thoracic and mediastinal disorders
Cough	2/10 (20%)
Hiccups	1/10 (10%)
Pharyngeal erythema	1/10 (10%)
Rhinorrhoea	1/10 (10%)
Throat irritation	1/10 (10%)
Upper respiratory tract inflammation	1/10 (10%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/10 (10%)
Pruritus	1/10 (10%)
Purpura	1/10 (10%)
Rash	2/10 (20%)
Skin hyperpigmentation	1/10 (10%)
Vascular disorders
Haemorrhage	1/10 (10%)
Hot flush	1/10 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.