Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator's Choice In Follicular Non-Hodgkin's Lymphoma (NHL)

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00562965
• Collaborator: UCB Pharma (Industry)
• Enrollment: 29
• Locations: 39
• Arms: 2
• Actual Duration (Months): 41
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This protocol is designed to assess the efficacy and safety of inotuzumab ozogamicin given with rituximab compared to a defined investigator's choice therapy. Subjects will be randomized to one of these two arms of the study.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Follicular	Drug: inotuzumab ozogamicin; Drug: rituximab; Drug: rituximab; Drug: cyclophosphamide; Drug: vincristine; Drug: prednisone/prednisolone; Drug: mitoxantrone; Drug: fludarabine; Drug: dexamethasone	Phase 3

Detailed Description

On January 14th 2009, enrollment in the study was discontinued because of poor enrollment and because it was unlikely that the study would meet the estimated enrollment of approximately 978 subjects. The decision was not prompted by the identification of any safety signals in this or other studies. Active treatment and follow-up of the already enrolled subjects was continued. On July, 22th 2010 , the study was amended to shorten the long-term follow-up to one year after active treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Health Services Research
• Official Title: An Open-label, Randomized, Phase 3 Study Of Inotuzumab Ozogamicin (Cmc-544) Administered In Combination With Rituximab Compared To A Defined Investigator's Choice Therapy In Subjects With Relapsed Or Refractory, Cd22- Positive, Follicular B-cell Non Hodgkin's Lymphoma
• Actual Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Subjects will receive rituximab intravenously at a dose level of 375 mg/m² on day 1 of each cycle followed by inotuzumab ozogamicin administered intravenously at a dose level of 1.8 mg/m2 on day 2. The sequence will be repeated every 28 days.	Drug: inotuzumab ozogamicin; IV administration, 1.8mg/m² on day 2 of each cycle every 28 days, for up to 8 cycles.; Drug: rituximab; IV administration, 375 mg/m² on day 1 of each cycle every 28 days, for up to 8 cycles.
Active Comparator: B Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5.	Drug: rituximab; intravenous rituximab at a dose of 375 mg/m2 on day 1; Drug: cyclophosphamide; intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1; Drug: vincristine; intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1; Drug: prednisone/prednisolone; oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5; Drug: mitoxantrone; mitoxantrone 10 mg/m2 intravenous on day 2; Drug: fludarabine; fludarabine 25 mg/m2 intravenous on days 2 through 4; Drug: dexamethasone; oral dexamethasone 20 mg/day on days 1-5

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [Baseline until disease progression or death or up to 1 year after last dose of study drug]

   PFS was defined as the time from randomization to disease progression or death due to any cause, whichever occurred first, censored at the last tumor evaluation date. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.44.

Secondary Outcome Measures

1. Percentage of Participants With Objective Response (OR) [Baseline, every 6 to 12 weeks during treatment period, end of treatment (EOT) (42 days after last dose), every 12 weeks during follow-up for up to 1 year after the last dose of study drug]

   OR was based on assessment of complete response(CR),unconfirmed CR(Cru),partial response(PR) as per International Response Criteria for Non-Hodgkin's Lymphoma.Confirmed response=response persists on repeat imaging at least 4 weeks after initial response.CR=complete disappearance of all detectable clinical/radiographic evidence of disease,lymph nodes regressed to normal size [at least 1.5 centimeter(cm) or less],spleen regressed,not palpable on physical examination,bone marrow infiltrate cleared on repeat aspiration/biopsy.PR=at least 50 percent (%) decrease in sum of product diameters of 6 greatest dominant nodes,no increase in other nodes,liver/spleen,no new sites of disease. CRu=residual lymph node greater than 1.5 cm in transverse diameter that has regressed more than 75% in product diameter.Individual nodes previously confluent,regressed more than 75% in product diameters.Indeterminate bone marrow (increased number/size of lymph aggregates without cytologic/architectural atypia).

2. Overall Survival Probability at Months 6, 12 and 24 [Baseline up to Month 6, 12, 24]

   Overall survival was defined as the time from randomization to death due to any cause, censoring at the date of last contact or the end of the study. Participants who withdrew or lost to follow-up from study without having death documented were censored at the date of last contact. Kaplan-Meier estimates of the probability of survival at 6, 12 and 24 months was used to estimate the survival function.

3. Pharmacokinetics of Inotuzumab Ozogamicin in Combination With Rituximab [0, 1, 168 hours on Cycle 1, 2; 0, 1, 2, 168 hours on Cycle 3, 4]

Other Outcome Measures

1. Number of Participants With Clinically Significant Change From Baseline in QT Interval Findings [Baseline up to 42 days post-treatment]

   Assessments of QT interval was performed only in rituximab + inotuzumab ozogamicinin group. QT interval corrected using Fridericia's formula (QTcF) and Bazett's formula (QTcB) was analyzed as per common terminology criteria for adverse events (CTCAE) version 3.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening or disabling AE, Grade 5 = death related to AE. Number of participants with change in CTCAE grading at post-baseline time point compared to the baseline were presented. The post-baseline value was defined as the maximum grade after the first dose date on or before the end of treatment.

2. Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) [Baseline up to 42 days post-treatment]

   AE=any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. TEAE=between first dose of study drug and up to 42 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

3. Number of Participants With Clinically Significant Change From Baseline in Laboratory Findings [Baseline up to 42 days post-treatment, disease follow up (every 12 weeks for a minimum of 1 year and up to 2 years)]

   Criteria for laboratory test abnormality: Blood Chemistry (alkaline phosphatase [greater than{>}5*upper limit of normal {ULN}, calcium [less than {<}1.75 millimole per liter {mmol/L}, creatinine [>3*ULN], glucose [>13.9 mmol/L], phosphorous [<0.6 mmol/L], potassium [<3 mmol/L], aspartate transaminase [>5.0*ULN], total bilirubin [>3*ULN]), Coagulation (international normalized ratio [>2*ULN]), Hematology (hemoglobin [<80 grams/Liter], lymphocytes [<0.5*10^9/L], absolute neutrophil count [<1*10^9/L], platelet count [<50*10^9/L], WBC [<2.0*10^9/L]).

4. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [Baseline up to 42 days post-treatment, disease follow up (every 12 weeks for a minimum of 1 year and up to 2 years)]

   Criteria for determining significant change from baseline in vital signs abnormalities: heart rate value of <40 beats per minute and value >150 beats per minute, systolic blood pressure (SBP) of <80 or >210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of <40 or >130 mmHg, temperature <32 or >40 degree centigrade, and body weight>=10% increase or decrease of body weight in kilogram (kg).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects with a diagnosis of CD20 and CD22-positive, follicular lymphoma, who have received 1 or 2 prior regimens, at least 1 of which should have contained administration of rituximab (either as a single agent or in combination).

• Age 18 years or older.

• ECOG performance status <= 2.

• ANC >= 1.5 x 10^{9/L (1500/mL) and platelets >= 75 x 10}9/L (75,000/mL), serum creatinine <= 1.5 x ULN and urine protein to creatinine ratio of <= 0.5, total bilirubin <= 1.5 x ULN, AST and ALT <= 2.5 x ULN.

• At least 1 measurable disease lesion that is >= 1.5 cm x 1.5 cm by CT or MRI, in an area of no prior radiation therapy, or documented progression in an area that was previously irradiated.

Exclusion Criteria:

• Subjects with clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b follicular lymphoma.

• Subjects whose disease is rituximab refractory, meaning that they did not have a CR or PR, or that they experienced disease progression within 6 months from the initiation of the rituximab or rituximab containing treatment regimen administered immediately preceding study enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Facey Medical Group	Mission Hills	California	United States	91345
2	Deaconess Clinic	Evansville	Indiana	United States	47713
3	The Harry & Jeanette Weinberg Cancer Inst at Franklin Square	Baltimore	Maryland	United States	21237
4	Newland Medical Associates	Novi	Michigan	United States	48374
5	Newland Medical Associates, PC	Southfield	Michigan	United States	48075
6	Park Nicollet Frauenshuh Cancer Center	Saint Louis Park	Minnesota	United States	55426
7	Hematology and Oncology Associates	Columbus	Mississippi	United States	39706
8	Hematology and Oncology Associates	Corinth	Mississippi	United States	38834
9	Hematology and Oncology Associates at Bridgepoint	Tupelo	Mississippi	United States	38801
10	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
11	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
12	Hematology Oncology Associates of Northern New Jersy	Morristown	New Jersey	United States	07960
13	Advanced Oncology Associates	Armonk	New York	United States	10504
14	Avi Einzing, MD	Bronx	New York	United States	10461
15	Advanced Oncology Associates	New Rochelle	New York	United States	10801
16	Marc Zimmerman, MD	Pomona	New York	United States	10970
17	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801
18	Centro de Transplantes de medula Osea de Rosario, CETRAMOR	Rosario	Santa FE	Argentina	S2000AYW
19	Universitair Ziekenhuis Gent	Gent		Belgium	9000
20	Oncologisch Centrum GZA - Location St. Augustinus	Wilrijk		Belgium	2610
21	Hopital Charles LeMoyne	Greenfield Park	Quebec	Canada	J4V 2H1
22	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
23	CHUS-Hopital Fleurimont	Sherbrooke	Quebec	Canada	J1H 5N4
24	C.H.A. Enfant-Jesus	Quebec		Canada	G1J 1Z4
25	Prince of Wales Hospital	Shatin	NEW Territories	Hong Kong
26	Queen Mary Hospital	Hong Kong		Hong Kong
27	Jehangir Clinical Development Centre	Pune	Maharashtra	India	411001
28	MMF Joshi Hospital and Ratna Memorial Hospital	Pune	Maharashtra	India	411004
29	B. P. Poddar Hospital and Medical Research Ltd.	Kolkata	WEST Bengal	India	700053
30	Divisione di Ematologia - Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
31	Yonsei University Health System-Severance Hospital	Seoul		Korea, Republic of	120-752
32	Hospital Universitario de Nuevo Leon	Monterrey	Nuevo LEON	Mexico	64460
33	Instytut Hematologii i Transfuzjologii	Warszawa		Poland	02-776
34	Hospitais Da Universidade De Coimbra	Coimbra		Portugal	3000-075
35	Moscow Regional Research Clinical Institute named after Vladimirsky	Moscow		Russian Federation	120110
36	Wits Donald Gordon Clinical Trial Site	Johannesburg	Gauteng	South Africa	2193
37	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid	Spain	28222
38	Hospital Santa Creu I Sant Pau	Barcelona		Spain	08041
39	Hospital de La Princesa	Madrid		Spain	28006

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: NCT00562965
• Other Study ID Numbers: 3129K4-3301; B1931006; 2007-000219-27
• First Posted: Nov 26, 2007
• Last Update Posted: Jan 9, 2018
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Dexamethasone; Prednisone; Prednisolone; Cyclophosphamide; Rituximab; Fludarabine; Vincristine; Mitoxantrone; Inotuzumab Ozogamicin

Study Results

Participant Flow

Recruitment Details	Enrollment of participants started on 15 November 2007 and completed on 16 January 2009. The trial was terminated (07 April 2011) due to poor accrual of 29 out of 978 planned participants.

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin	Control Regimens R-CVP + R-FND
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.	Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.
Period Title: Overall Study
STARTED	15	14
Treated	15	13
COMPLETED	12	8
NOT COMPLETED	3	6

Baseline Characteristics

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin	Control Regimens R-CVP + R-FND	Total
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.	Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.	Total of all reporting groups
Overall Participants	15	14	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.3 (11.4)	60.9 (12.4)	61.7 (11.7)
Sex: Female, Male (Count of Participants)
Female	9 60%	6 42.9%	15 51.7%
Male	6 40%	8 57.1%	14 48.3%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time from randomization to disease progression or death due to any cause, whichever occurred first, censored at the last tumor evaluation date. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.44.
Time Frame	Baseline until disease progression or death or up to 1 year after last dose of study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all participants who were randomized in to the study.

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin	Control Regimens R-CVP + R-FND
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.	Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.
Measure Participants	15	14
Median (95% Confidence Interval) [months]	NA	16.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab + Inotuzumab Ozogamicin, Control Regimens R-CVP + R-FND
	Comments	To detect a hazard ratio of 0.77 with 85% power using a 2-sided log-rank test at the 5% significance level, it was planned that approximately 978 participants were needed to be randomized but due to premature termination only 29 participants were randomized.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0358
	Comments
	Method	Cox proportional hazard regression model
	Comments	A 2-sided 5% significance level on a stratified Cox proportional hazard regression model was used.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; 0.04 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	In this regression model, treatment arm was the covariate and the strata (number of prior regimens, investigator's choice of therapy and geographical region) over which participants were stratified prior to randomization were the variables.

2. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	OR was based on assessment of complete response(CR),unconfirmed CR(Cru),partial response(PR) as per International Response Criteria for Non-Hodgkin's Lymphoma.Confirmed response=response persists on repeat imaging at least 4 weeks after initial response.CR=complete disappearance of all detectable clinical/radiographic evidence of disease,lymph nodes regressed to normal size [at least 1.5 centimeter(cm) or less],spleen regressed,not palpable on physical examination,bone marrow infiltrate cleared on repeat aspiration/biopsy.PR=at least 50 percent (%) decrease in sum of product diameters of 6 greatest dominant nodes,no increase in other nodes,liver/spleen,no new sites of disease. CRu=residual lymph node greater than 1.5 cm in transverse diameter that has regressed more than 75% in product diameter.Individual nodes previously confluent,regressed more than 75% in product diameters.Indeterminate bone marrow (increased number/size of lymph aggregates without cytologic/architectural atypia).
Time Frame	Baseline, every 6 to 12 weeks during treatment period, end of treatment (EOT) (42 days after last dose), every 12 weeks during follow-up for up to 1 year after the last dose of study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all participants who were randomized in to the study.

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin	Control Regimens R-CVP + R-FND
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.	Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.
Measure Participants	15	14
Number (95% Confidence Interval) [percentage of participants]	93.3 622%	64.3 459.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab + Inotuzumab Ozogamicin, Control Regimens R-CVP + R-FND
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0801
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Overall Survival Probability at Months 6, 12 and 24
Description	Overall survival was defined as the time from randomization to death due to any cause, censoring at the date of last contact or the end of the study. Participants who withdrew or lost to follow-up from study without having death documented were censored at the date of last contact. Kaplan-Meier estimates of the probability of survival at 6, 12 and 24 months was used to estimate the survival function.
Time Frame	Baseline up to Month 6, 12, 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all participants who were randomized in to the study.

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin	Control Regimens R-CVP + R-FND
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.	Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.
Measure Participants	15	14
Overall Survival: Baseline up to Month 6	100.0	92.3
Overall Survival: Baseline up to Month 12	86.7	83.9
Overall Survival: Baseline up to Month 24	86.7	67.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab + Inotuzumab Ozogamicin, Control Regimens R-CVP + R-FND
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1727
	Comments
	Method	Cox proportional hazard regression model
	Comments	Stratified Cox proportional hazard regression model was utilized.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; 0.05 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	In this regression model, treatment arm was the covariate and the strata (number of prior regimens, investigator's choice of therapy and geographical region) over which participants were stratified prior to randomization were the variables.

4. Secondary Outcome

Title	Pharmacokinetics of Inotuzumab Ozogamicin in Combination With Rituximab
Time Frame	0, 1, 168 hours on Cycle 1, 2; 0, 1, 2, 168 hours on Cycle 3, 4

Outcome Measure Data

Analysis Population Description

Data for this outcome measurement was not collected since pharmacokinetic parameters were not analyzed in this study due to very few number of participants with PK samples.

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin	Control Regimens R-CVP + R-FND
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.	Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.
Measure Participants	0	0

5. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in QT Interval Findings
Description	Assessments of QT interval was performed only in rituximab + inotuzumab ozogamicinin group. QT interval corrected using Fridericia's formula (QTcF) and Bazett's formula (QTcB) was analyzed as per common terminology criteria for adverse events (CTCAE) version 3.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening or disabling AE, Grade 5 = death related to AE. Number of participants with change in CTCAE grading at post-baseline time point compared to the baseline were presented. The post-baseline value was defined as the maximum grade after the first dose date on or before the end of treatment.
Time Frame	Baseline up to 42 days post-treatment

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of a test article. Here 'N' signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.
Measure Participants	9
QTcB: BL normal, post-BL normal	4 26.7%
QTcB: BL normal, post-BL Grade 1	2 13.3%
QTcB: BL normal, post-BL Grade 2	3 20%
QTcF: BL normal, post-BL normal	6 40%
QTcF: BL normal, post-BL Grade 1	3 20%

6. Other Pre-specified Outcome

Title	Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs)
Description	AE=any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. TEAE=between first dose of study drug and up to 42 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame	Baseline up to 42 days post-treatment

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of a test article (either rituximab + inotuzumab ozogamicin or control regimens R-CVP + R-FND).

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin	Control Regimens R-CVP + R-FND
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.	Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.
Measure Participants	15	13
Number [participants]	12 80%	13 92.9%

7. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Laboratory Findings
Description	Criteria for laboratory test abnormality: Blood Chemistry (alkaline phosphatase [greater than{>}5*upper limit of normal {ULN}, calcium [less than {<}1.75 millimole per liter {mmol/L}, creatinine [>3*ULN], glucose [>13.9 mmol/L], phosphorous [<0.6 mmol/L], potassium [<3 mmol/L], aspartate transaminase [>5.0*ULN], total bilirubin [>3*ULN]), Coagulation (international normalized ratio [>2*ULN]), Hematology (hemoglobin [<80 grams/Liter], lymphocytes [<0.5*10^9/L], absolute neutrophil count [<1*10^9/L], platelet count [<50*10^9/L], WBC [<2.0*10^9/L]).
Time Frame	Baseline up to 42 days post-treatment, disease follow up (every 12 weeks for a minimum of 1 year and up to 2 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of a test article (either rituximab + inotuzumab ozogamicin or control regimens R-CVP + R-FND).

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin	Control Regimens R-CVP + R-FND
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.	Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.
Measure Participants	15	13
Baseline up to 42 days post-treatment	11 73.3%	12 85.7%
Disease follow up	8 53.3%	7 50%

8. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Description	Criteria for determining significant change from baseline in vital signs abnormalities: heart rate value of <40 beats per minute and value >150 beats per minute, systolic blood pressure (SBP) of <80 or >210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of <40 or >130 mmHg, temperature <32 or >40 degree centigrade, and body weight>=10% increase or decrease of body weight in kilogram (kg).
Time Frame	Baseline up to 42 days post-treatment, disease follow up (every 12 weeks for a minimum of 1 year and up to 2 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of a test article (either rituximab + inotuzumab ozogamicin or control regimens R-CVP + R-FND).

Arm/Group Title	Rituximab + Inotuzumab Ozogamicin	Control Regimens R-CVP + R-FND
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.	Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.
Measure Participants	15	13
Baseline up to 42 days post-treatment	0 0%	1 7.1%
Disease follow up	3 20%	2 14.3%

Adverse Events

Time Frame	Baseline up to 42 days post--treatment
Adverse Event Reporting Description	Same event may appear as both AE and SAE, the presented events are distinct.Event may be serious in 1 subject and nonserious in another,or 1 subject may have experienced both SAE and non-SAE during study.TEAE=from first study drug dose up to 42 days after last dose,were absent before treatment or that worsened relative to pretreatment state.
Arm/Group Title	Rituximab + Inotuzumab Ozogamicin		Control Regimens R-CVP + R-FND
Arm/Group Description	Participants received intravenous infusion of rituximab 375 milligram per square meter (mg/m^2) of body surface area (BSA) on Day 1 followed by intravenous infusion of inotuzumab ozogamicin (CMC-544) 1.8 mg/m^2 of BSA on Day 2 for each cycle up to 8 cycles. Each cycle was of 28 days.		Participants received either regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA along with intravenous infusion of cyclophosphamide 750 mg/m^2 of BSA and vincristine 1.4 mg/m^2 of BSA on Day 1 followed by oral prednisone/prednisolone 40 mg/m^2 of BSA on Days 1 through 5 for up to 8 cycles (R-CVP); or regimen containing intravenous infusion of rituximab 375 mg/m^2 of BSA on Day 1 followed by intravenous infusion of novantrone (mitoxantrone) 10 mg/m^2 of BSA on Day 2, intravenous infusion of fludarabine 25 mg/m^2 of BSA on Days 2 through 4, and oral dexamethasone 20 mg once daily on Days 1 through 5 for up to 8 cycles (R-FND). Each regimen cycle was of 21 days.
All Cause Mortality
	Rituximab + Inotuzumab Ozogamicin		Control Regimens R-CVP + R-FND
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rituximab + Inotuzumab Ozogamicin		Control Regimens R-CVP + R-FND
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/15 (40%)		6/13 (46.2%)
Blood and lymphatic system disorders
Febrile neutropenia	0/15 (0%)		3/13 (23.1%)
Leukopenia	0/15 (0%)		1/13 (7.7%)
Neutropenia	0/15 (0%)		2/13 (15.4%)
Thrombocytopenia	0/15 (0%)		1/13 (7.7%)
Gastrointestinal disorders
Abdominal pain	1/15 (6.7%)		0/13 (0%)
General disorders
Asthenia	0/15 (0%)		1/13 (7.7%)
Chills	1/15 (6.7%)		0/13 (0%)
Pyrexia	0/15 (0%)		1/13 (7.7%)
Hepatobiliary disorders
Venoocclusive liver disease	1/15 (6.7%)		0/13 (0%)
Infections and infestations
Cellulitis	1/15 (6.7%)		0/13 (0%)
Lower respiratory tract infection	0/15 (0%)		1/13 (7.7%)
Pneumonia	0/15 (0%)		2/13 (15.4%)
Pneumonia cryptococcal	1/15 (6.7%)		0/13 (0%)
Sepsis	1/15 (6.7%)		1/13 (7.7%)
Viral infection	0/15 (0%)		1/13 (7.7%)
Investigations
Blood creatinine increased	1/15 (6.7%)		0/13 (0%)
Gamma-glutamyltransferase increased	1/15 (6.7%)		0/13 (0%)
Lipase increased	1/15 (6.7%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/15 (0%)		1/13 (7.7%)
Lung infiltration	1/15 (6.7%)		0/13 (0%)
Respiratory failure	0/15 (0%)		1/13 (7.7%)
Other (Not Including Serious) Adverse Events
	Rituximab + Inotuzumab Ozogamicin		Control Regimens R-CVP + R-FND
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/15 (100%)		13/13 (100%)
Blood and lymphatic system disorders
Anaemia	2/15 (13.3%)		7/13 (53.8%)
Febrile neutropenia	0/15 (0%)		1/13 (7.7%)
Hypercoagulation	0/15 (0%)		1/13 (7.7%)
Leukocytosis	2/15 (13.3%)		0/13 (0%)
Leukopenia	2/15 (13.3%)		5/13 (38.5%)
Lymph node pain	1/15 (6.7%)		0/13 (0%)
Lymphopenia	2/15 (13.3%)		2/13 (15.4%)
Monocytosis	1/15 (6.7%)		0/13 (0%)
Neutropenia	5/15 (33.3%)		11/13 (84.6%)
Thrombocytopenia	8/15 (53.3%)		7/13 (53.8%)
Cardiac disorders
Atrial fibrillation	0/15 (0%)		1/13 (7.7%)
Extrasystoles	1/15 (6.7%)		0/13 (0%)
Palpitations	2/15 (13.3%)		1/13 (7.7%)
Supraventricular extrasystoles	1/15 (6.7%)		0/13 (0%)
Supraventricular tachycardia	1/15 (6.7%)		0/13 (0%)
Ear and labyrinth disorders
Ear pain	0/15 (0%)		1/13 (7.7%)
Eye disorders
Eye disorder	1/15 (6.7%)		0/13 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/15 (6.7%)		0/13 (0%)
Abdominal pain	5/15 (33.3%)		0/13 (0%)
Abdominal pain lower	0/15 (0%)		1/13 (7.7%)
Abdominal pain upper	1/15 (6.7%)		0/13 (0%)
Aphthous stomatitis	0/15 (0%)		1/13 (7.7%)
Constipation	3/15 (20%)		2/13 (15.4%)
Diarrhoea	2/15 (13.3%)		5/13 (38.5%)
Dry mouth	1/15 (6.7%)		0/13 (0%)
Dyspepsia	1/15 (6.7%)		2/13 (15.4%)
Dysphagia	0/15 (0%)		1/13 (7.7%)
Gastric ulcer	0/15 (0%)		1/13 (7.7%)
Gastritis	0/15 (0%)		1/13 (7.7%)
Gastrooesophageal reflux disease	1/15 (6.7%)		0/13 (0%)
Mouth ulceration	1/15 (6.7%)		0/13 (0%)
Nausea	4/15 (26.7%)		7/13 (53.8%)
Oesophagitis	1/15 (6.7%)		0/13 (0%)
Oral pain	1/15 (6.7%)		0/13 (0%)
Stomatitis	1/15 (6.7%)		1/13 (7.7%)
Vomiting	2/15 (13.3%)		1/13 (7.7%)
General disorders
Asthenia	2/15 (13.3%)		0/13 (0%)
Chest pain	1/15 (6.7%)		0/13 (0%)
Chills	3/15 (20%)		0/13 (0%)
Fatigue	6/15 (40%)		3/13 (23.1%)
Feeling cold	1/15 (6.7%)		0/13 (0%)
Generalised oedema	1/15 (6.7%)		0/13 (0%)
Influenza like illness	1/15 (6.7%)		0/13 (0%)
Malaise	0/15 (0%)		1/13 (7.7%)
Mucosal inflammation	0/15 (0%)		1/13 (7.7%)
Oedema	1/15 (6.7%)		0/13 (0%)
Oedema peripheral	1/15 (6.7%)		1/13 (7.7%)
Pain	1/15 (6.7%)		2/13 (15.4%)
Pyrexia	6/15 (40%)		3/13 (23.1%)
Thirst	1/15 (6.7%)		0/13 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	4/15 (26.7%)		3/13 (23.1%)
Infections and infestations
Bronchitis	1/15 (6.7%)		0/13 (0%)
Cystitis	1/15 (6.7%)		0/13 (0%)
Device related infection	0/15 (0%)		1/13 (7.7%)
Ear infection	0/15 (0%)		1/13 (7.7%)
Folliculitis	0/15 (0%)		1/13 (7.7%)
Fungal infection	0/15 (0%)		1/13 (7.7%)
Herpes zoster	0/15 (0%)		1/13 (7.7%)
Influenza	1/15 (6.7%)		2/13 (15.4%)
Localised infection	1/15 (6.7%)		0/13 (0%)
Nasopharyngitis	1/15 (6.7%)		2/13 (15.4%)
Pharyngotonsillitis	1/15 (6.7%)		0/13 (0%)
Pneumonia	1/15 (6.7%)		1/13 (7.7%)
Rhinitis	0/15 (0%)		1/13 (7.7%)
Sinusitis	0/15 (0%)		1/13 (7.7%)
Upper respiratory tract infection	0/15 (0%)		2/13 (15.4%)
Urinary tract infection	1/15 (6.7%)		0/13 (0%)
Vulvovaginal mycotic infection	0/15 (0%)		1/13 (7.7%)
Injury, poisoning and procedural complications
Excoriation	1/15 (6.7%)		0/13 (0%)
Fall	1/15 (6.7%)		0/13 (0%)
Infusion related reaction	0/15 (0%)		1/13 (7.7%)
Procedural pain	1/15 (6.7%)		0/13 (0%)
Investigations
Activated partial thromboplastin time prolonged	0/15 (0%)		1/13 (7.7%)
Alanine aminotransferase increased	4/15 (26.7%)		2/13 (15.4%)
Aspartate aminotransferase increased	6/15 (40%)		2/13 (15.4%)
Bilirubin conjugated increased	1/15 (6.7%)		0/13 (0%)
Blood albumin decreased	2/15 (13.3%)		2/13 (15.4%)
Blood albumin increased	1/15 (6.7%)		0/13 (0%)
Blood alkaline phosphatase increased	5/15 (33.3%)		2/13 (15.4%)
Blood amylase increased	1/15 (6.7%)		0/13 (0%)
Blood bicarbonate decreased	1/15 (6.7%)		0/13 (0%)
Blood bicarbonate increased	1/15 (6.7%)		0/13 (0%)
Blood calcium decreased	1/15 (6.7%)		2/13 (15.4%)
Blood chloride decreased	1/15 (6.7%)		0/13 (0%)
Blood chloride increased	1/15 (6.7%)		0/13 (0%)
Blood creatinine decreased	1/15 (6.7%)		0/13 (0%)
Blood glucose increased	1/15 (6.7%)		3/13 (23.1%)
Blood lactate dehydrogenase decreased	2/15 (13.3%)		1/13 (7.7%)
Blood lactate dehydrogenase increased	3/15 (20%)		1/13 (7.7%)
Blood phosphorus decreased	0/15 (0%)		1/13 (7.7%)
Blood phosphorus increased	2/15 (13.3%)		3/13 (23.1%)
Blood potassium decreased	0/15 (0%)		3/13 (23.1%)
Blood sodium decreased	1/15 (6.7%)		2/13 (15.4%)
Blood sodium increased	1/15 (6.7%)		0/13 (0%)
Blood urea decreased	2/15 (13.3%)		0/13 (0%)
Blood urea increased	2/15 (13.3%)		2/13 (15.4%)
Blood uric acid decreased	1/15 (6.7%)		0/13 (0%)
Blood uric acid increased	0/15 (0%)		1/13 (7.7%)
Gamma-glutamyltransferase increased	3/15 (20%)		0/13 (0%)
Haemoglobin decreased	1/15 (6.7%)		1/13 (7.7%)
Lymphocyte count decreased	1/15 (6.7%)		0/13 (0%)
Neutrophil count	0/15 (0%)		1/13 (7.7%)
Neutrophil count decreased	0/15 (0%)		1/13 (7.7%)
PCO2 decreased	1/15 (6.7%)		0/13 (0%)
PCO2 increased	1/15 (6.7%)		0/13 (0%)
Protein total decreased	2/15 (13.3%)		1/13 (7.7%)
Red blood cell count decreased	1/15 (6.7%)		0/13 (0%)
Urine output decreased	1/15 (6.7%)		1/13 (7.7%)
White blood cell count decreased	0/15 (0%)		1/13 (7.7%)
Metabolism and nutrition disorders
Acidosis	0/15 (0%)		1/13 (7.7%)
Decreased appetite	4/15 (26.7%)		3/13 (23.1%)
Dehydration	1/15 (6.7%)		0/13 (0%)
Fluid overload	0/15 (0%)		1/13 (7.7%)
Hyperglycaemia	1/15 (6.7%)		1/13 (7.7%)
Hypoalbuminaemia	0/15 (0%)		1/13 (7.7%)
Hypocalcaemia	2/15 (13.3%)		1/13 (7.7%)
Hypochloraemia	0/15 (0%)		1/13 (7.7%)
Hypokalaemia	5/15 (33.3%)		4/13 (30.8%)
Hypomagnesaemia	0/15 (0%)		1/13 (7.7%)
Hyponatraemia	1/15 (6.7%)		0/13 (0%)
Hypoproteinaemia	0/15 (0%)		1/13 (7.7%)
Hypouricaemia	1/15 (6.7%)		0/13 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/15 (0%)		2/13 (15.4%)
Back pain	2/15 (13.3%)		0/13 (0%)
Bone pain	0/15 (0%)		2/13 (15.4%)
Flank pain	0/15 (0%)		1/13 (7.7%)
Groin pain	1/15 (6.7%)		1/13 (7.7%)
Mobility decreased	1/15 (6.7%)		0/13 (0%)
Musculoskeletal chest pain	1/15 (6.7%)		1/13 (7.7%)
Myalgia	2/15 (13.3%)		0/13 (0%)
Pain in jaw	0/15 (0%)		1/13 (7.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/15 (6.7%)		0/13 (0%)
Nervous system disorders
Dizziness	0/15 (0%)		1/13 (7.7%)
Dysgeusia	0/15 (0%)		2/13 (15.4%)
Headache	6/15 (40%)		2/13 (15.4%)
Memory impairment	1/15 (6.7%)		0/13 (0%)
Neuropathy peripheral	0/15 (0%)		2/13 (15.4%)
Paraesthesia	1/15 (6.7%)		0/13 (0%)
Peripheral sensory neuropathy	3/15 (20%)		1/13 (7.7%)
Psychomotor hyperactivity	0/15 (0%)		1/13 (7.7%)
Psychiatric disorders
Insomnia	1/15 (6.7%)		3/13 (23.1%)
Renal and urinary disorders
Chromaturia	1/15 (6.7%)		0/13 (0%)
Dysuria	1/15 (6.7%)		0/13 (0%)
Haematuria	2/15 (13.3%)		0/13 (0%)
Micturition urgency	1/15 (6.7%)		0/13 (0%)
Pollakiuria	1/15 (6.7%)		0/13 (0%)
Proteinuria	1/15 (6.7%)		0/13 (0%)
Renal failure	0/15 (0%)		1/13 (7.7%)
Reproductive system and breast disorders
Epididymitis	1/15 (6.7%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	7/15 (46.7%)		5/13 (38.5%)
Dyspnoea	2/15 (13.3%)		3/13 (23.1%)
Dyspnoea exertional	1/15 (6.7%)		0/13 (0%)
Epistaxis	4/15 (26.7%)		0/13 (0%)
Haemoptysis	1/15 (6.7%)		0/13 (0%)
Oropharyngeal pain	1/15 (6.7%)		1/13 (7.7%)
Paranasal sinus hypersecretion	1/15 (6.7%)		1/13 (7.7%)
Productive cough	1/15 (6.7%)		2/13 (15.4%)
Rhinorrhoea	0/15 (0%)		1/13 (7.7%)
Sinus congestion	1/15 (6.7%)		1/13 (7.7%)
Skin and subcutaneous tissue disorders
Alopecia	0/15 (0%)		2/13 (15.4%)
Hyperhidrosis	0/15 (0%)		1/13 (7.7%)
Night sweats	1/15 (6.7%)		0/13 (0%)
Pigmentation disorder	0/15 (0%)		1/13 (7.7%)
Pruritus	1/15 (6.7%)		0/13 (0%)
Rash	1/15 (6.7%)		0/13 (0%)
Rash macular	1/15 (6.7%)		0/13 (0%)
Skin lesion	2/15 (13.3%)		0/13 (0%)
Vascular disorders
Hot flush	1/15 (6.7%)		0/13 (0%)
Hypertension	2/15 (13.3%)		0/13 (0%)
Hypotension	0/15 (0%)		1/13 (7.7%)
Subclavian vein thrombosis	0/15 (0%)		1/13 (7.7%)

Limitations/Caveats

Study did not met estimated enrollment of approximately 978 participants,thus analysis and conclusions were limited by small number of enrolled participants.Termination was not prompted by identification of safety concerns with inotuzumab ozogamicin.

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.