Trial Outcomes & Findings for Study Evaluating Chemotherapy in Combination With Inotuzumab Ozogamicin In Subjects With Non-Hodgkin's Lymphoma (NCT NCT01055496)

Last Updated: 2019-08-02

Results Overview

DLT was defined as: febrile neutropenia, Grade (Gr) 4 neutropenia ≥7 days, Gr 4 thrombocytopenia ≥7 days, Gr 3/4 thrombocytopenia associated with bleeding requiring a transfusion, Gr 3/4 non-hematologic toxicity (except alopecia) ≥7 days or treatment-related and clinically significant irrespective of duration, ≥Gr 3 QTc prolongation, Gr 4 alanine or aspartate aminotransferase, Gr 2 hyperbilirubinemia (greater than (\>)1.5 x upper normal limit) \>7 days, delayed recovery from a treatment-related toxicity that prevented re-dosing by \>7 days, or Granulocyte-colony stimulating factor treatment during the first cycle.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

103 participants

Primary outcome timeframe

From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.

Results posted on

2019-08-02

Participant Flow

Screening included CD-20 \& CD-22 immunophenotyping of NHL, international prognostic index or follicular lymphoma international prognostic index score, B-symptom and lymphoma evaluation, Eastern Cooperative Oncology Group performance status, left ventricular ejection fraction assessment, computed tomography scans, bone marrow aspirate and/or biopsy.

Participant milestones

Participant milestones
Measure	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin IV inotuzumab ozogamicn (0.8 or 1.3 mg/m\^2 on Day 2 of each 21-day cycle) in combination with rituximab (375 mg/m\^2) and vincristine (1.4mg/m\^2) administererd IV on day 1, prednisone (40mg/m\^2) PO on Day 1-5 and cyclophosphamid IV (375, 550 or 750 mg/m\^2) on Day 1 of each 21-day cycle (R-CVP) for a maximum of 6 cycles.	Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin IV inotuzumab ozogamicin (0.8 mg/m\^2 on Day 2 of each 21-day cycle) in combination with IV Rituximab (375 mg/m\^2 on Day 1), dexamethasone (40 mg PO on Days 1 to 4), and escalating doses of IV gemcitabine (500 or 1000 mg/m\^2) or IV cisplatinum (0, 37.5, 50 or 75 mg/m\^2) on Day 1 of each 21-day cycle (R-GDP) for a maximum of 6 cycles.
Overall Study STARTED	48	55
Overall Study COMPLETED	33	25
Overall Study NOT COMPLETED	15	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin IV inotuzumab ozogamicn (0.8 or 1.3 mg/m\^2 on Day 2 of each 21-day cycle) in combination with rituximab (375 mg/m\^2) and vincristine (1.4mg/m\^2) administererd IV on day 1, prednisone (40mg/m\^2) PO on Day 1-5 and cyclophosphamid IV (375, 550 or 750 mg/m\^2) on Day 1 of each 21-day cycle (R-CVP) for a maximum of 6 cycles.	Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin IV inotuzumab ozogamicin (0.8 mg/m\^2 on Day 2 of each 21-day cycle) in combination with IV Rituximab (375 mg/m\^2 on Day 1), dexamethasone (40 mg PO on Days 1 to 4), and escalating doses of IV gemcitabine (500 or 1000 mg/m\^2) or IV cisplatinum (0, 37.5, 50 or 75 mg/m\^2) on Day 1 of each 21-day cycle (R-GDP) for a maximum of 6 cycles.
Overall Study Withdrawal by Subject	2	4
Overall Study Death	13	23
Overall Study Lost to Follow-up	0	2
Overall Study Other - Unspecified	0	1

Baseline Characteristics

Study Evaluating Chemotherapy in Combination With Inotuzumab Ozogamicin In Subjects With Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin n=48 Participants IV inotuzumab ozogamicn (0.8 or 1.3 mg/m\^2 on Day 2 of each 21-day cycle) in combination with rituximab (375 mg/m\^2) and vincristine (1.4mg/m\^2) administererd IV on day 1, prednisone (40mg/m\^2) PO on Day 1-5 and cyclophosphamid IV (375, 550 or 750 mg/m\^2) on Day 1 of each 21-day cycle (R-CVP) for a maximum of 6 cycles.	Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin n=55 Participants IV inotuzumab ozogamicin (0.8 mg/m\^2 on Day 2 of each 21-day cycle) in combination with IV Rituximab (375 mg/m\^2 on Day 1), dexamethasone (40 mg PO on Days 1 to 4), and escalating doses of IV gemcitabine (500 or 1000 mg/m\^2) or IV cisplatinum (0, 37.5, 50 or 75 mg/m\^2) on Day 1 of each 21-day cycle (R-GDP) for a maximum of 6 cycles.	Total n=103 Participants Total of all reporting groups
Age, Continuous	62.2 Years STANDARD_DEVIATION 9.0 • n=5 Participants	62.1 Years STANDARD_DEVIATION 11.8 • n=7 Participants	62.2 Years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	18 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	37 Participants n=7 Participants	64 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.

Population: Safety Analysis Population includes all subjects who received at least 1 cycle of study drug. Analysis population for DLT is participants evaluable for DLT.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=3 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=3 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 n=6 Participants Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 n=4 Participants Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 n=10 Participants Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Participants Reporting Dose Limiting Toxicity (DLT) Adverse Events (AEs) for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 1	0 Participants	0 Participants	1 Participants	2 Participants	2 Participants	—

PRIMARY outcome

Timeframe: From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.

Population: Safety Analysis Population includes all subjects who received at least 1 cycle of study drug. Analysis population for DLT is participants evaluable for DLT.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=6 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=3 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 n=8 Participants Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 n=4 Participants Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 n=6 Participants Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 n=10 Participants Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Participants Reporting DLT AEs for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 2	0 Participants	2 Participants	1 Participants	2 Participants	0 Participants	3 Participants

PRIMARY outcome

Timeframe: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks.

Population: Intent-to-Treat (ITT) population: all participants enrolled into the study

OR was evaluated according to the International Response Criteria for NHLs. CR was defined as complete disappearance of all lesions and disease-related symptoms; all nodes must have decreased to normal (less than or equal to \[≤\]1.5 centimeters \[cm\] in their greatest transverse diameter (GTD) for nodes \>1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy. PR was defined as \>50% decrease in the sum of the product diameters (SPD) of up to 6 index lesions. No increase in size of other nodes, liver or spleen. Splenic and hepatic nodules must have regressed by ≥50% in the SPD or GTD (for single nodules). With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=32 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=28 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Percentage of Participants With Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) According to International Response Criteria for NHLs in the MTD and EE Cohorts	81.3 Percentage of participants Interval 63.56 to 92.79	53.6 Percentage of participants Interval 33.87 to 72.49	—	—	—	—

PRIMARY outcome

Timeframe: SAEs were assessed from informed consent through and including the end of treatment visit (at least 28 calendar days after last study drug administration). Non-SAEs were recorded from time of the first dose of study drug through last participant visit.

Population: Safety population - included all participants who received ≥1 cycle of investigational product

An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event may not necessarily have had a causal relationship with the treatment or usage. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were defined as those occurring on or after the first study drug dose day through and including 56 days post last dose of study drug. The severity of all AEs was graded by the investigator using the National Cancer Institute Common Terminology Criteria for AE Version 3.0 (NCI CTCAE v3.0).

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=48 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=55 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Percentage of Participants With a Treatment Emergent AE Subjects with AEs	100 Percentage of Participants	100 Percentage of Participants	—	—	—	—
Percentage of Participants With a Treatment Emergent AE Subjects with SAEs	31.3 Percentage of Participants	45.5 Percentage of Participants	—	—	—	—
Percentage of Participants With a Treatment Emergent AE Subjects with Grade 3 or 4 AEs	89.6 Percentage of Participants	96.4 Percentage of Participants	—	—	—	—
Percentage of Participants With a Treatment Emergent AE Subjects with Grade 5 AEs	4.2 Percentage of Participants	5.5 Percentage of Participants	—	—	—	—
Percentage of Participants With a Treatment Emergent AE Subjects discontinued due to AEs	27.1 Percentage of Participants	36.4 Percentage of Participants	—	—	—	—
Percentage of Participants With a Treatment Emergent AE Subjects with dose reduced due to AEs	16.7 Percentage of Participants	32.7 Percentage of Participants	—	—	—	—
Percentage of Participants With a Treatment Emergent AE Subjects with temporary discontinuation due to AEs	54.2 Percentage of Participants	67.3 Percentage of Participants	—	—	—	—

PRIMARY outcome

Timeframe: Within 3 days prior to the start of each cycle, on Day 8 of each cycle, on Day 15 of Cycles 1, 2, and 3, and the end-of-treatment visit. Each Cycle is 21 Days.

Population: Safety population

The following parameters were analyzed for blood chemistry: blood urea nitrogen (or urea), creatinine, glucose, calcium, sodium, potassium, phosphorus, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, total bilirubin (and direct bilirubin, if total bilirubin was elevated), alkaline phosphatase, uric acid (or urate), albumin and total protein. Laboratory test results were graded using the NCI CTCAE v3.0 where CTCAE Grade 3 equals "severe" and CTCAE Grade 4 equals "life threatening or disabling."

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=48 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=55 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Percentage of Participants With Any Grade 3/4 Chemistry Abnormality During Therapy	21.3 Percentage of Participants	36.4 Percentage of Participants	—	—	—	—

PRIMARY outcome

Timeframe: Within 3 days prior to the start of each cycle, Day 8 of each cycle, Day 15 of Cycles 1, 2, and 3, and the end-of-treatment visit. Each Cycle is 21 Days.

Population: Safety population

The following parameters were analyzed for hematology: lymphocytes, basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, monocytes, neutrophils, platelets, prothrombin international normalized ratio, prothrombin time, fibrinogen, and activated partial thromboplastin time. Laboratory test results were graded using the NCI CTCAE v3.0 where CTCAE Grade 3 equals "severe" and CTCAE Grade 4 equals "life threatening or disabling."

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=48 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=55 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Percentage of Participants With Any Grade 3/4 Hematology Abnormality During Therapy	91.7 Percentage of Participants	96.4 Percentage of Participants	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks.

Population: ITT population

OR was evaluated according to the International Response Criteria for NHLs. CR was defined as complete disappearance of all lesions and disease-related symptoms; all nodes must have decreased to normal (≤1.5 cm in their GTD for nodes \>1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy. PR was defined as \>50% decrease in the SPD of up to 6 index lesions. No increase in size of other nodes, liver or spleen. Splenic and hepatic nodules must have regressed by ≥50% in the SPD or GTD (for single nodules). With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=16 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=27 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Percentage of Participants With a Best OR of CR or PR According to International Response Criteria for NHLs in the DE Cohorts	81.3 Percentage of participants Interval 54.35 to 95.95	51.9 Percentage of participants Interval 31.95 to 71.33	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks

Population: ITT population

PFS was defined as time from date of first dose to the earlier date of progression (including symptomatic deterioration), date of death from any cause, or initiation of new anticancer therapy for the lymphoma. Participants without an event were censored at the date of the last valid tumour assessment. A valid tumour assessment visit was defined as the tumour assessment visit with overall response of CR, PR, stable disease (SD), or disease progression (PD), but not 'Not Done' or 'Unknown'. Participants without a post-baseline tumour assessment and without a PFS event were censored on the date of first dose.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=16 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=27 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Kaplan-Meier Estimate of the Progression-Free Survival (PFS) in the DE Cohorts	16.36 Months Interval 4.4 to 23.39	10.12 Months Interval 3.45 to 28.16	—	—	—	—

SECONDARY outcome

Timeframe: 6, 12 and 24 months

Population: ITT population

Measure includes death from any cause, PD (including symptomatic deterioration) during and after treatment or initiation of new anticancer therapy for the lymphoma. PD was defined as symptomatic deterioration and according to the International Response Criteria for NHL: 1) appearance of any new lesion \>1.5 cm in any axis during or at EOT, even if other lesions are decreasing, 2) at least a 50% increase from nadir in the SPD of any previously involved or single involved nodes, or the size of other lesions (splenic or hepatic). Lymph nodes with a short axis diameter of \<1.0 cm must increase by ≥50% and to a size of 1.5x1.5 cm or \>1.5 cm in the long axis, 3) 50% increase in the longest diameter of any single previously identified node \>1 cm in its short axis. PD was defined as clinical PD, new non-nodal lesions or new nodal lesion ≥1.5 cm in GTD, progression of existing non-index lesions or bone marrow that was negative and now positive.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=16 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=27 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the DE Cohorts 6 months	80.00 Percent Probability Interval 49.98 to 93.07	60.98 Percent Probability Interval 39.42 to 76.89	—	—	—	—
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the DE Cohorts 12 months	66.67 Percent Probability Interval 37.53 to 84.56	47.92 Percent Probability Interval 27.41 to 65.82	—	—	—	—
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the DE Cohorts 24 months	22.22 Percent Probability Interval 4.64 to 47.87	33.54 Percent Probability Interval 15.58 to 52.63	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study medication through 2 year follow-up period, including but not limited to planned assessments scheduled every 9 to 24 weeks

Population: ITT population

PFS was defined as time from date of first dose to the earlier date of progression (including symptomatic deterioration), date of death from any cause, or initiation of new anticancer therapy for the lymphoma. Participants without an event were censored at the date of the last valid tumour assessment. A valid tumour assessment visit was defined as the tumour assessment visit with OR of CR, PR, SD, or PD, but not 'Not Done' or 'Unknown'. Participants without a post-baseline tumour assessment and without a PFS event were censored on the date of first dose.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=32 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=28 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Kaplan-Meier Estimate of the PFS in the MTD Confirmation/EE Cohorts	14.36 Months Interval 5.13 to NA means upper limit for 95% CI could not be estimated due to insufficient events observed.	6.14 Months Interval 4.44 to 10.64	—	—	—	—

SECONDARY outcome

Timeframe: 6, 12, and 24 months

Population: ITT population

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=32 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=28 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts. 6 months	61.85 Percent Probability Interval 42.66 to 76.26	54.74 Percent Probability Interval 31.9 to 72.77	—	—	—	—
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts. 12 months	51.54 Percent Probability Interval 32.83 to 67.41	24.88 Percent Probability Interval 9.15 to 44.52	—	—	—	—
Kaplan-Meier Estimates of the Probability of Being Alive and Free From PD or New Anticancer Therapy at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts. 24 months	44.67 Percent Probability Interval 26.73 to 61.12	NA Percent Probability NA means the corresponding parameters could not be estimated due to insufficient events observed.	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study medication through 2 year follow-up period

Population: ITT population

OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=16 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=27 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Kaplan-Meier Estimate of the Overall Survival (OS) in the DE Cohorts	NA Months Interval 11.7 to NA means the corresponding parameters could not be estimated due to insufficient events observed.	NA Months Interval 7.03 to NA means the corresponding parameters could not be estimated due to insufficient events observed.	—	—	—	—

SECONDARY outcome

Timeframe: 6, 12, and 24 months

Population: ITT population

OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=16 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=27 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the DE Cohorts 6 months	100.00 Percent Probability Interval 100.0 to 100.0	74.07 Percent Probability Interval 53.19 to 86.7	—	—	—	—
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the DE Cohorts 12 months	80.00 Percent Probability Interval 49.98 to 93.07	62.96 Percent Probability Interval 42.12 to 78.07	—	—	—	—
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the DE Cohorts 24 months	80.00 Percent Probability Interval 49.98 to 93.07	55.09 Percent Probability Interval 34.62 to 71.53	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study medication through 2 year follow-up period

Population: ITT population

OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=32 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=28 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Kaplan-Meier Estimate of the OS in the MTD Confirmation/EE Cohorts	NA Months Interval 24.51 to NA means the corresponding parameters could not be estimated due to insufficient events observed.	NA Months Interval 8.38 to NA means the corresponding parameters could not be estimated due to insufficient events observed.	—	—	—	—

SECONDARY outcome

Timeframe: 6, 12, and 24 Months

Population: ITT population

OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=32 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=28 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts 6 months	84.38 Percent Probability Interval 66.46 to 93.18	88.00 Percent Probability Interval 67.26 to 95.96	—	—	—	—
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts 12 months	78.13 Percent Probability Interval 59.52 to 88.92	59.11 Percent Probability Interval 37.29 to 75.56	—	—	—	—
Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts 24 months	71.61 Percent Probability Interval 52.51 to 84.11	53.74 Percent Probability Interval 31.82 to 71.4	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose on Cycle 1, Day 2; Pre-dose, 1 and 3 hours post-dose on Cycle 3, Day 2; 24 hours post-dose on Cycle 3, Day 3 and 168 hours post-dose on Cycle 3, Day 8.

Population: PK population - included all participants who provided samples for PK analysis.

Pharmacokinetic (PK) samples were required for participants enrolled in the confirmatory and preliminary efficacy MTD cohorts only (Parts 2 and 3). Concentrations of inotuzumab ozogamicin in serum were determined using appropriate, validated unconjugated (also known as free) bioanalytical assays.

Outcome measures

Outcome measures
Measure	Cohort 1, Arm 1 n=4 Participants Participants in cohort 1 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in with combination rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 375 mg/m\^2.	Cohort 2, Arm 1 n=6 Participants Participants in cohort 2 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 550 mg/m\^2.	Cohort 3, Arm 1 n=4 Participants Participants in cohort 3 of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	Cohort 4, Arm 1 n=6 Participants Participants in cohort 4 of Arm 1 received inotuzumab ozogamicin (1.3 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV on Day 1 at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 1 n=38 Participants Participants in the MTD of Arm 1 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2) and vincristine (1.4 mg/m\^2) administered IV on Day 1, prednisone (40 mg/m\^2) PO on Days 1 to 5 and cyclophosphamide IV at a dose of 750 mg/m\^2.	MTD Confirmation Cohort, Arm 2 n=36 Participants Participants in the MTD cohort of Arm 2 received inotuzumab ozogamicin (0.8 mg/m\^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with rituximab (375 mg/m\^2), cisplatinum (50 mg/m\^2) and gemcitabine (500 mg/m\^2) IV on Day 1, and dexamethasone (40 mg) PO on Days 1 to 4 of each 21-day cycle.
Mean Inotuzumab Ozogamicin Serum Concentrations Cycle 1 Day 2, 0h	NA ng/mL Standard Deviation NA Summary statistics are not presented as number of observations above lower limit of quantification (NALQ) = 0.	NA ng/mL Standard Deviation NA Summary statistics are not presented as number of observations above lower limit of quantification (NALQ) = 0.	NA ng/mL Standard Deviation NA Summary statistics are not presented as number of observations above lower limit of quantification (NALQ) = 0.	NA ng/mL Standard Deviation NA Summary statistics are not presented as number of observations above lower limit of quantification (NALQ) = 0.	NA ng/mL Standard Deviation NA Summary statistics are not presented as number of observations above lower limit of quantification (NALQ) = 0.	NA ng/mL Standard Deviation NA Summary statistics are not presented as number of observations above lower limit of quantification (NALQ) = 0.
Mean Inotuzumab Ozogamicin Serum Concentrations Cycle 3 Day 2, 0h	—	—	—	—	NA ng/mL Standard Deviation NA Summary statistics are not presented as number of observations above lower limit of quantification (NALQ) = 0.	25.00 ng/mL Standard Deviation 76.151
Mean Inotuzumab Ozogamicin Serum Concentrations Cycle 3 Day 2, 1h	—	—	—	—	189.74 ng/mL Standard Deviation 81.528	283.27 ng/mL Standard Deviation 127.151
Mean Inotuzumab Ozogamicin Serum Concentrations Cycle 3 Day 2, 3h	—	—	—	—	213.95 ng/mL Standard Deviation 71.692	280.33 ng/mL Standard Deviation 119.12
Mean Inotuzumab Ozogamicin Serum Concentrations Cycle 3 Day 3, 24h	—	—	—	—	110.39 ng/mL Standard Deviation 37.468	154.25 ng/mL Standard Deviation 81.608
Mean Inotuzumab Ozogamicin Serum Concentrations Cycle 3 Day 8, 168h	—	—	—	—	NA ng/mL Standard Deviation NA Summary statistics are not presented as number of observations above lower limit of quantification (NALQ) = 0.	NA ng/mL Standard Deviation NA Summary statistics are not presented as number of observations above lower limit of quantification (NALQ) = 0.

Adverse Events

Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin

Serious events: 15 serious events

Other events: 48 other events

Deaths: 0 deaths

Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin

Serious events: 25 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60