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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01055496
• Collaborator: UCB Pharma (Industry)
• Enrollment: 103
• Locations: 28
• Arms: 2
• Actual Duration (Months): 48
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a phase 1 trial designed to evaluate safety and tolerability of chemotherapy in combination with inotuzumab ozogamicin, an investigational product, in adults with CD22-positive non-Hodgkin's lymphoma. The trial will involve two arms. In one arm, subjects will receive chemotherapy regimen R-CVP (rituximab, cyclophosphamide, vincristine and prednisone). In the other arm, subjects will receive R-GDP (rituximab, gemcitabine, cisplatinum and dexamethasone). Subjects in both arms will also receive inotuzumab ozogamicin.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, B-Cell	Drug: inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone; Drug: inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Non-Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: AN OPEN-LABEL, PHASE 1 STUDY OF R-CVP OR R-GDP IN COMBINATION WITH INOTUZUMAB OZOGAMICIN IN SUBJECTS WITH CD22-POSTIVE NON-HODGKIN'S LYMPHOMA
• Actual Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 (R-CVP) Subjects in arm 1 will be enrolled in dose escalation cohorts that will initially evaluate an escalating dose of cyclophosphamide in combination with set doses of inotuzumab ozogamicin, vincristine, prednisone, and rituximab.	Drug: inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone; Day 1: Rituximab at 375 mg/m2 Cyclophosphamide at 375 mg/m2 (cohort 1), 550mg/m2 (cohort 2), 750 mg/m2 (cohort 3, 4) Vincristine at 1.4 mg/m2 (max 2 mg) Day 2 Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2, 3), 1.3 mg/m2 (cohort 4) Days 1-5: Prednisone at 40 mg/m2 Each cycle is 3 weeks, with a maximum of 6 cycles total.; Other Names: CMC-544
Experimental: Arm 2 (R-GDP) Subjects in arm 2 will be enrolled in dose escalation cohorts that will initially evaluate escalating doses of gemcitabine and/or cisplatinum in combination with set doses of inotuzumab ozogamicin, dexamethasone, and rituximab.	Drug: inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone; Day 1: Rituximab at 375 mg/m2 Gemcitabine at 500 mg/m2 (cohort 1, 2b, 3b), 1000mg/m2 (cohort 2a, 3a, 4, 5) Cisplatin at 37.5 mg/m2 (cohort 1, 2a), 50mg/m2 (cohort 2b, 3a), 75mg/m2 (cohort 3b, 4, 5) Day 2: Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2a, 2b, 3a, 3b, 4), 1.3mg/m2 (cohort 5) Days 1-4: Dexamethasone at 40 mg Each cycle is 3 weeks, with a maximum of 6 cycles total.; Other Names: CMC-544

Outcome Measures

Primary Outcome Measures

1. Participants Reporting Dose Limiting Toxicity (DLT) Adverse Events (AEs) for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 1 [From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.]

   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.

2. Participants Reporting DLT AEs for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 2 [From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.]

   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.

3. 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 [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.]

   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.

4. Percentage of Participants With a Treatment Emergent AE [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.]

   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).

5. Percentage of Participants With Any Grade 3/4 Chemistry Abnormality During Therapy [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.]

   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."

6. Percentage of Participants With Any Grade 3/4 Hematology Abnormality During Therapy [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.]

   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."

Secondary Outcome Measures

1. Percentage of Participants With a Best OR of CR or PR According to International Response Criteria for NHLs in the DE Cohorts [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.]

   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.

2. Kaplan-Meier Estimate of the Progression-Free Survival (PFS) in the DE Cohorts [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]

   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.

3. 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, 12 and 24 months]

   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.

4. Kaplan-Meier Estimate of the PFS in the MTD Confirmation/EE Cohorts [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]

   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.

5. 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, 12, and 24 months]

   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.

6. Kaplan-Meier Estimate of the Overall Survival (OS) in the DE Cohorts [From first dose of study medication through 2 year follow-up period]

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

7. Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the DE Cohorts [6, 12, and 24 months]

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

8. Kaplan-Meier Estimate of the OS in the MTD Confirmation/EE Cohorts [From first dose of study medication through 2 year follow-up period]

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

9. Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts [6, 12, and 24 Months]

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

10. Mean Inotuzumab Ozogamicin Serum Concentrations [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.]

    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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Dose escalation cohorts: subjects with diagnosis of CD22-positive Non-Hodgkin's Lymphoma (NHL) who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy.

• Expanded maximum tolerated dose (MTD) confirmation and preliminary efficacy cohorts: subjects with diagnosis of CD22-positive NHL who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy or newly diagnosed subjects who are not candidates for anthracycline-based therapy.

• At least 1 measurable disease lesion that is > 1 cm in the longest transverse diameter, with a product of the diameters > 2.25 cm2 by CT or magnetic resonance imaging (MRI).

Exclusion Criteria:

• Candidate for potentially curative therapy such as stem cell transplantation.

• Prior allogeneic hematopoietic stem cell transplantation (HSCT).

• Prior autologous transplantation, radioimmunotherapy, or other anti CD22 immunotherapy <= 6 months before the first dose of investigational product.

• More than 3 previous combination chemotherapy (2 or more cytotoxics) anticancer regimens.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Davis Cancer Pavillion and Shands Medical Plaza	Gainesville	Florida	United States	32608
2	Shands Cancer Hospital At The University Of Florida	Gainesville	Florida	United States	32608
3	Shands Hospital at the University of Florida	Gainesville	Florida	United States	32610
4	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111-2497
5	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
6	Northwest Medical Specialties, PLLC	Federal Way	Washington	United States	98003
7	Northwest Medical Specialties, PLLC	Gig Harbor	Washington	United States	98332
8	Northwest Medical Specialties, PLLC	Lakewood	Washington	United States	98499
9	Rainier Physicians, PC	Puyallup	Washington	United States	98373
10	Northwest Medical Specialties PLLC	Tacoma	Washington	United States	98405
11	UZ Gent	Gent		Belgium	9000
12	UZ Gasthuisberg	Leuven		Belgium	3000
13	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
14	Queen Elizabeth Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
15	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
16	Hospital Saint-Louis - Service d'Hemato-Oncologie	Paris Cedex 10		France	75475
17	Hopital Saint-Louis -Universite Paris VII	Paris		France	75010
18	Centre Hospitalier Lyon Sud - Service d'Hematologie	Pierre Benite		France	69495
19	Prince of Wales Hospital	Hong Kong		Hong Kong
20	Nagoya Daini Red Cross Hospital	Nagoya	Aichi	Japan	466-8650
21	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
22	Cancer Institute Hospital, Japanese Foundation For Cancer Research	Koto-Ku	Tokyo	Japan	135-8550
23	Samsung Medical Center	Seoul		Korea, Republic of	135-710
24	Singapore General Hospital	Singapore		Singapore	169608
25	Nuffield Hospital	Eastleigh	Hants	United Kingdom	SO53 2DW
26	Spire Southampton Hospital	Southampton	Hants	United Kingdom	SO16 6UY
27	Cancer Sciences Division, Somers Cancer Research Building	Southampton	Hants	United Kingdom	SO16 6YD
28	Guy's and St Thomas' NHS Foundation Trust	London		United Kingdom	SE1 9RT

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: NCT01055496
• Other Study ID Numbers: 3129K2-1105; B1931003; 2009-015497-35
• First Posted: Jan 25, 2010
• Last Update Posted: Aug 2, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Pfizer: Non-Hodgkin's lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Gemcitabine; Dexamethasone; Prednisone; Cyclophosphamide; Rituximab; Vincristine; Cisplatin; Inotuzumab Ozogamicin

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin	Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	48	55
COMPLETED	33	25
NOT COMPLETED	15	30

Baseline Characteristics

Arm/Group Title	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin	Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	48	55	103
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.2 (9.0)	62.1 (11.8)	62.2 (10.6)
Sex: Female, Male (Count of Participants)
Female	21 43.8%	18 32.7%	39 37.9%
Male	27 56.3%	37 67.3%	64 62.1%

Outcome Measures

1. Primary Outcome

Title	Participants Reporting Dose Limiting Toxicity (DLT) Adverse Events (AEs) for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 1
Description	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.
Time Frame	From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1, Arm 1	Cohort 2, Arm 1	Cohort 3, Arm 1	Cohort 4, Arm 1	MTD Confirmation Cohort, Arm 1
Arm/Group Description	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.	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.	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.	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.	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.
Measure Participants	3	3	6	4	10
Count of Participants [Participants]	0 0%	0 0%	1 1%	2 NaN	2 NaN

2. Secondary Outcome

Title	Percentage of Participants With a Best OR of CR or PR According to International Response Criteria for NHLs in the DE Cohorts
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	DE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	DE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received inotuzumab ozogamicin (0.8 or 1.3 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with R-CVP. Rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) were administered IV on Day 1, prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at escalating doses of 375, 550, or 750 mg/m^2 on Day 1, of each 21-day cycle for a maximum of 6 cycles, according to a 3+3 DE rule where the doses escalated in a step-by-step fashion to determine the MTD.	Participants 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 R-GDP. Rituximab (375 mg/m^2) was administered IV on Day 1 and dexamethasone (40 mg) PO on Days 1 to 4. Participants received escalating doses of gemcitabine (500 or 1000 mg/m^2) or cisplatinum (0, 37.5, 50 or 75 mg/m^2) and were administered IV on Day 1 of each 21-day cycle, for a maximum of 6 cycles. DE in Arm 2 was conducted using an up-and-down dose escalation method by increasing or decreasing the dose of either cisplatinum or gemcitabine to determine the MTD.
Measure Participants	16	27
Number (95% Confidence Interval) [Percentage of participants]	81.3 169.4%	51.9 94.4%

3. Primary Outcome

Title	Participants Reporting DLT AEs for Participants in the DE Cohort and the MTD Confirmation Cohort for Arm 2
Description	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.
Time Frame	From the first dose of study medication (Study Day 1) to the completion of the first 21-day cycle.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1, Arm 2	Cohort 2a, Arm 2	Cohort 2b, Arm 2	Cohort 3b, Arm 2	Cohort 4, Arm 2	MTD Confirmation Cohort, Arm 2
Arm/Group Description	Participants in cohort 1 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) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and gemcitabine (500 mg/m^2) and cisplatinum (37.5 mg/m^2) administered IV on Day 1 of each 21-day cycle.	Participants in cohort 2a 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) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and gemcitabine (1000 mg/m^2) and cisplatinum (37.5 mg/m^2) administered IV on Day 1 of each 21-day cycle.	Participants in cohort 2b 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) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and gemcitabine (500 mg/m^2) and cisplatinum (50 mg/m^2) administered IV on Day 1 of each 21-day cycle.	Participants in cohort 3b 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) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and gemcitabine (500 mg/m^2) and cisplatinum (75 mg/m^2) administered IV on Day 1 of each 21-day cycle.	Participants in cohort 4 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) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and gemcitabine (1000 mg/m^2) administered IV on Day 1 of each 21-day cycle.	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.
Measure Participants	6	3	8	4	6	10
Count of Participants [Participants]	0 0%	2 3.6%	1 1%	2 NaN	0 NaN	3 NaN

4. Primary Outcome

Title	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
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	MTD/EE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	MTD/EE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) IV on Day 1, inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 and prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at 750 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 6 cycles.	Participants received rituximab (375 mg/m^2), cisplatinum (50 mg/m^2) and gemcitabine (500 mg/m^2) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles.
Measure Participants	32	28
Number (95% Confidence Interval) [Percentage of participants]	81.3 169.4%	53.6 97.5%

5. Secondary Outcome

Title	Kaplan-Meier Estimate of the Progression-Free Survival (PFS) in the DE Cohorts
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	DE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	DE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received inotuzumab ozogamicin (0.8 or 1.3 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with R-CVP. Rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) were administered IV on Day 1, prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at escalating doses of 375, 550, or 750 mg/m^2 on Day 1, of each 21-day cycle for a maximum of 6 cycles, according to a 3+3 DE rule where the doses escalated in a step-by-step fashion to determine the MTD.	Participants 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 R-GDP. Rituximab (375 mg/m^2) was administered IV on Day 1 and dexamethasone (40 mg) PO on Days 1 to 4. Participants received escalating doses of gemcitabine (500 or 1000 mg/m^2) or cisplatinum (0, 37.5, 50 or 75 mg/m^2) and were administered IV on Day 1 of each 21-day cycle, for a maximum of 6 cycles. DE in Arm 2 was conducted using an up-and-down dose escalation method by increasing or decreasing the dose of either cisplatinum or gemcitabine to determine the MTD.
Measure Participants	16	27
Median (95% Confidence Interval) [Months]	16.36	10.12

6. Secondary Outcome

Title	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
Description	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.
Time Frame	6, 12 and 24 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	DE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	DE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received inotuzumab ozogamicin (0.8 or 1.3 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with R-CVP. Rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) were administered IV on Day 1, prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at escalating doses of 375, 550, or 750 mg/m^2 on Day 1, of each 21-day cycle for a maximum of 6 cycles, according to a 3+3 DE rule where the doses escalated in a step-by-step fashion to determine the MTD.	Participants 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 R-GDP. Rituximab (375 mg/m^2) was administered IV on Day 1 and dexamethasone (40 mg) PO on Days 1 to 4. Participants received escalating doses of gemcitabine (500 or 1000 mg/m^2) or cisplatinum (0, 37.5, 50 or 75 mg/m^2) and were administered IV on Day 1 of each 21-day cycle, for a maximum of 6 cycles. DE in Arm 2 was conducted using an up-and-down dose escalation method by increasing or decreasing the dose of either cisplatinum or gemcitabine to determine the MTD.
Measure Participants	16	27
6 months	80.00	60.98
12 months	66.67	47.92
24 months	22.22	33.54

7. Secondary Outcome

Title	Kaplan-Meier Estimate of the PFS in the MTD Confirmation/EE Cohorts
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	MTD/EE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	MTD/EE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) IV on Day 1, inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 and prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at 750 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 6 cycles.	Participants received rituximab (375 mg/m^2), cisplatinum (50 mg/m^2) and gemcitabine (500 mg/m^2) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles.
Measure Participants	32	28
Median (95% Confidence Interval) [Months]	14.36	6.14

8. Secondary Outcome

Title	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.
Description	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.
Time Frame	6, 12, and 24 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	MTD/EE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	MTD/EE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) IV on Day 1, inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 and prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at 750 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 6 cycles.	Participants received rituximab (375 mg/m^2), cisplatinum (50 mg/m^2) and gemcitabine (500 mg/m^2) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles.
Measure Participants	32	28
6 months	61.85	54.74
12 months	51.54	24.88
24 months	44.67	NA

9. Secondary Outcome

Title	Kaplan-Meier Estimate of the Overall Survival (OS) in the DE Cohorts
Description	OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.
Time Frame	From first dose of study medication through 2 year follow-up period

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	DE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	DE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received inotuzumab ozogamicin (0.8 or 1.3 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with R-CVP. Rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) were administered IV on Day 1, prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at escalating doses of 375, 550, or 750 mg/m^2 on Day 1, of each 21-day cycle for a maximum of 6 cycles, according to a 3+3 DE rule where the doses escalated in a step-by-step fashion to determine the MTD.	Participants 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 R-GDP. Rituximab (375 mg/m^2) was administered IV on Day 1 and dexamethasone (40 mg) PO on Days 1 to 4. Participants received escalating doses of gemcitabine (500 or 1000 mg/m^2) or cisplatinum (0, 37.5, 50 or 75 mg/m^2) and were administered IV on Day 1 of each 21-day cycle, for a maximum of 6 cycles. DE in Arm 2 was conducted using an up-and-down dose escalation method by increasing or decreasing the dose of either cisplatinum or gemcitabine to determine the MTD.
Measure Participants	16	27
Median (95% Confidence Interval) [Months]	NA	NA

10. Secondary Outcome

Title	Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the DE Cohorts
Description	OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.
Time Frame	6, 12, and 24 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	DE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	DE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received inotuzumab ozogamicin (0.8 or 1.3 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles in combination with R-CVP. Rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) were administered IV on Day 1, prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at escalating doses of 375, 550, or 750 mg/m^2 on Day 1, of each 21-day cycle for a maximum of 6 cycles, according to a 3+3 DE rule where the doses escalated in a step-by-step fashion to determine the MTD.	Participants 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 R-GDP. Rituximab (375 mg/m^2) was administered IV on Day 1 and dexamethasone (40 mg) PO on Days 1 to 4. Participants received escalating doses of gemcitabine (500 or 1000 mg/m^2) or cisplatinum (0, 37.5, 50 or 75 mg/m^2) and were administered IV on Day 1 of each 21-day cycle, for a maximum of 6 cycles. DE in Arm 2 was conducted using an up-and-down dose escalation method by increasing or decreasing the dose of either cisplatinum or gemcitabine to determine the MTD.
Measure Participants	16	27
6 months	100.00	74.07
12 months	80.00	62.96
24 months	80.00	55.09

11. Secondary Outcome

Title	Kaplan-Meier Estimate of the OS in the MTD Confirmation/EE Cohorts
Description	OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.
Time Frame	From first dose of study medication through 2 year follow-up period

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	MTD/EE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	MTD/EE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) IV on Day 1, inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 and prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at 750 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 6 cycles.	Participants received rituximab (375 mg/m^2), cisplatinum (50 mg/m^2) and gemcitabine (500 mg/m^2) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles.
Measure Participants	32	28
Median (95% Confidence Interval) [Months]	NA	NA

12. Secondary Outcome

Title	Kaplan-Meier Estimates of the Probability of Being Alive at 6, 12, and 24 Months in the MTD Confirmation/EE Cohorts
Description	OS was defined from date of first dose to date of death due to any cause, censoring at the date of last contact.
Time Frame	6, 12, and 24 Months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	MTD/EE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	MTD/EE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	Participants received rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) IV on Day 1, inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 and prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at 750 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 6 cycles.	Participants received rituximab (375 mg/m^2), cisplatinum (50 mg/m^2) and gemcitabine (500 mg/m^2) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles.
Measure Participants	32	28
6 months	84.38	88.00
12 months	78.13	59.11
24 months	71.61	53.74

13. Primary Outcome

Title	Percentage of Participants With a Treatment Emergent AE
Description	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).
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin	Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	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.	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.
Measure Participants	48	55
Subjects with AEs	100 208.3%	100 181.8%
Subjects with SAEs	31.3 65.2%	45.5 82.7%
Subjects with Grade 3 or 4 AEs	89.6 186.7%	96.4 175.3%
Subjects with Grade 5 AEs	4.2 8.8%	5.5 10%
Subjects discontinued due to AEs	27.1 56.5%	36.4 66.2%
Subjects with dose reduced due to AEs	16.7 34.8%	32.7 59.5%
Subjects with temporary discontinuation due to AEs	54.2 112.9%	67.3 122.4%

14. Primary Outcome

Title	Percentage of Participants With Any Grade 3/4 Chemistry Abnormality During Therapy
Description	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."
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin	Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	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.	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.
Measure Participants	48	55
Number [Percentage of Participants]	21.3 44.4%	36.4 66.2%

15. Primary Outcome

Title	Percentage of Participants With Any Grade 3/4 Hematology Abnormality During Therapy
Description	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."
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin	Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	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.	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.
Measure Participants	48	55
Number [Percentage of Participants]	91.7 191%	96.4 175.3%

16. Secondary Outcome

Title	Mean Inotuzumab Ozogamicin Serum Concentrations
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 4, Arm 1	Cohort 1, Arm 2	Cohort 3b, Arm 2	Cohort 4, Arm 2	Cohort 3/MTD/EE Arm 1: (R-CVP) Plus Inotuzumab Ozogamicin	Cohort 2b/MTD/EE Arm 2: (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	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.	Participants in cohort 1 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) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and gemcitabine (500 mg/m^2) and cisplatinum (37.5 mg/m^2) administered IV on Day 1 of each 21-day cycle.	Participants in cohort 3b 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) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and gemcitabine (500 mg/m^2) and cisplatinum (75 mg/m^2) administered IV on Day 1 of each 21-day cycle.	Participants in cohort 4 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) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and gemcitabine (1000 mg/m^2) administered IV on Day 1 of each 21-day cycle.	Participants received rituximab (375 mg/m^2) and vincristine (1.4 mg/m^2) IV on Day 1, inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2, prednisone (40 mg/m^2) PO on Days 1 to 5 and cyclophosphamide IV at 750 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 6 cycles.	Participants received rituximab (375 mg/m^2), cisplatinum (50 mg/m^2) and gemcitabine (500 mg/m^2) IV on Day 1, dexamethasone (40 mg) PO on Days 1 to 4, and inotuzumab ozogamicin (0.8 mg/m^2) IV on Day 2 of each 21-day cycle for a maximum of 6 cycles.
Measure Participants	4	6	4	6	38	36
Cycle 1 Day 2, 0h	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)
Cycle 3 Day 2, 0h	NA (NA)	25.00 (76.151)
Cycle 3 Day 2, 1h	189.74 (81.528)	283.27 (127.151)
Cycle 3 Day 2, 3h	213.95 (71.692)	280.33 (119.12)
Cycle 3 Day 3, 24h	110.39 (37.468)	154.25 (81.608)
Cycle 3 Day 8, 168h	NA (NA)	NA (NA)

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	Presented SAEs & AEs are treatment-emergent events (occurring on or after first study drug dose through and including 56 days post last dose of study drug).
Arm/Group Title	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin		Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin
Arm/Group Description	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.		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.
All Cause Mortality
	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin		Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin		Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/48 (31.3%)		25/55 (45.5%)
Blood and lymphatic system disorders
Anaemia	0/48 (0%)		1/55 (1.8%)
Febrile neutropenia	2/48 (4.2%)		7/55 (12.7%)
Neutropenia	1/48 (2.1%)		2/55 (3.6%)
Thrombocytopenia	0/48 (0%)		6/55 (10.9%)
Endocrine disorders
Adrenal insufficiency	0/48 (0%)		1/55 (1.8%)
Gastrointestinal disorders
Diarrhoea	0/48 (0%)		1/55 (1.8%)
Enteritis	1/48 (2.1%)		0/55 (0%)
Gastric ulcer	0/48 (0%)		1/55 (1.8%)
Gastrointestinal haemorrhage	0/48 (0%)		1/55 (1.8%)
Intestinal obstruction	0/48 (0%)		1/55 (1.8%)
Mallory-Weiss syndrome	1/48 (2.1%)		0/55 (0%)
Nausea	1/48 (2.1%)		0/55 (0%)
Oesophageal obstruction	0/48 (0%)		1/55 (1.8%)
Vomiting	1/48 (2.1%)		1/55 (1.8%)
General disorders
Device occlusion	1/48 (2.1%)		0/55 (0%)
Disease progression	0/48 (0%)		2/55 (3.6%)
Fatigue	0/48 (0%)		1/55 (1.8%)
Pain	0/48 (0%)		1/55 (1.8%)
Pyrexia	3/48 (6.3%)		3/55 (5.5%)
Hepatobiliary disorders
Cholangitis	0/48 (0%)		1/55 (1.8%)
Cholecystitis	1/48 (2.1%)		0/55 (0%)
Drug-induced liver injury	1/48 (2.1%)		0/55 (0%)
Hepatitis acute	1/48 (2.1%)		0/55 (0%)
Venoocclusive liver disease	0/48 (0%)		1/55 (1.8%)
Infections and infestations
Corynebacterium infection	0/48 (0%)		1/55 (1.8%)
Herpes zoster	1/48 (2.1%)		0/55 (0%)
Neutropenic sepsis	0/48 (0%)		3/55 (5.5%)
Pneumonia	1/48 (2.1%)		3/55 (5.5%)
Pneumonia pneumococcal	1/48 (2.1%)		0/55 (0%)
Pyelonephritis	1/48 (2.1%)		0/55 (0%)
Pyelonephritis acute	1/48 (2.1%)		0/55 (0%)
Rhinovirus infection	0/48 (0%)		1/55 (1.8%)
Sepsis	1/48 (2.1%)		0/55 (0%)
Urosepsis	1/48 (2.1%)		0/55 (0%)
Injury, poisoning and procedural complications
Humerus fracture	1/48 (2.1%)		0/55 (0%)
Infusion related reaction	0/48 (0%)		1/55 (1.8%)
Subdural haematoma	0/48 (0%)		1/55 (1.8%)
Metabolism and nutrition disorders
Dehydration	0/48 (0%)		1/55 (1.8%)
Hypercalcaemia	1/48 (2.1%)		0/55 (0%)
Hypokalaemia	0/48 (0%)		1/55 (1.8%)
Tumour lysis syndrome	0/48 (0%)		1/55 (1.8%)
Musculoskeletal and connective tissue disorders
Bursitis	0/48 (0%)		1/55 (1.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/48 (0%)		1/55 (1.8%)
Transitional cell carcinoma metastatic	0/48 (0%)		1/55 (1.8%)
Renal and urinary disorders
Haematuria	0/48 (0%)		1/55 (1.8%)
Pollakiuria	1/48 (2.1%)		0/55 (0%)
Renal failure	0/48 (0%)		1/55 (1.8%)
Renal failure acute	1/48 (2.1%)		0/55 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/48 (2.1%)		0/55 (0%)
Hypoxia	1/48 (2.1%)		0/55 (0%)
Lung disorder	1/48 (2.1%)		0/55 (0%)
Productive cough	1/48 (2.1%)		0/55 (0%)
Pulmonary embolism	0/48 (0%)		1/55 (1.8%)
Skin and subcutaneous tissue disorders
Toxic skin eruption	0/48 (0%)		1/55 (1.8%)
Vascular disorders
Jugular vein thrombosis	0/48 (0%)		1/55 (1.8%)
Thrombophlebitis	0/48 (0%)		1/55 (1.8%)
Other (Not Including Serious) Adverse Events
	Arm 1 (R-CVP) Plus Inotuzumab Ozogamicin		Arm 2 (R-GDP) Plus Inotuzumab Ozogamicin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/48 (100%)		55/55 (100%)
Blood and lymphatic system disorders
Anaemia	12/48 (25%)		24/55 (43.6%)
Leukopenia	31/48 (64.6%)		15/55 (27.3%)
Lymphopenia	28/48 (58.3%)		17/55 (30.9%)
Neutropenia	36/48 (75%)		38/55 (69.1%)
Thrombocytopenia	40/48 (83.3%)		46/55 (83.6%)
Cardiac disorders
Tachycardia	2/48 (4.2%)		3/55 (5.5%)
Gastrointestinal disorders
Abdominal discomfort	5/48 (10.4%)		2/55 (3.6%)
Abdominal distension	0/48 (0%)		4/55 (7.3%)
Abdominal pain	5/48 (10.4%)		7/55 (12.7%)
Abdominal pain lower	0/48 (0%)		3/55 (5.5%)
Abdominal pain upper	2/48 (4.2%)		6/55 (10.9%)
Ascites	1/48 (2.1%)		5/55 (9.1%)
Constipation	29/48 (60.4%)		24/55 (43.6%)
Diarrhoea	8/48 (16.7%)		12/55 (21.8%)
Dry mouth	3/48 (6.3%)		3/55 (5.5%)
Dyspepsia	1/48 (2.1%)		3/55 (5.5%)
Gastritis	4/48 (8.3%)		3/55 (5.5%)
Gastrooesophageal reflux disease	1/48 (2.1%)		4/55 (7.3%)
Haemorrhoids	3/48 (6.3%)		0/55 (0%)
Nausea	21/48 (43.8%)		25/55 (45.5%)
Stomatitis	5/48 (10.4%)		8/55 (14.5%)
Vomiting	10/48 (20.8%)		13/55 (23.6%)
General disorders
Asthenia	4/48 (8.3%)		6/55 (10.9%)
Chest pain	3/48 (6.3%)		0/55 (0%)
Chills	2/48 (4.2%)		9/55 (16.4%)
Fatigue	24/48 (50%)		29/55 (52.7%)
Malaise	9/48 (18.8%)		1/55 (1.8%)
Mucosal inflammation	1/48 (2.1%)		3/55 (5.5%)
Oedema	3/48 (6.3%)		2/55 (3.6%)
Oedema peripheral	4/48 (8.3%)		11/55 (20%)
Pyrexia	9/48 (18.8%)		16/55 (29.1%)
Hepatobiliary disorders
Hyperbilirubinaemia	18/48 (37.5%)		5/55 (9.1%)
Liver disorder	10/48 (20.8%)		4/55 (7.3%)
Immune system disorders
Drug hypersensitivity	5/48 (10.4%)		0/55 (0%)
Hypersensitivity	3/48 (6.3%)		0/55 (0%)
Infections and infestations
Nasopharyngitis	5/48 (10.4%)		1/55 (1.8%)
Oral candidiasis	3/48 (6.3%)		1/55 (1.8%)
Pneumonia	1/48 (2.1%)		3/55 (5.5%)
Upper respiratory tract infection	5/48 (10.4%)		8/55 (14.5%)
Urinary tract infection	4/48 (8.3%)		2/55 (3.6%)
Injury, poisoning and procedural complications
Contusion	4/48 (8.3%)		4/55 (7.3%)
Fall	4/48 (8.3%)		2/55 (3.6%)
Infusion related reaction	4/48 (8.3%)		2/55 (3.6%)
Investigations
Alanine aminotransferase increased	17/48 (35.4%)		5/55 (9.1%)
Aspartate aminotransferase increased	21/48 (43.8%)		11/55 (20%)
Blood alkaline phosphatase increased	13/48 (27.1%)		6/55 (10.9%)
Blood lactate dehydrogenase increased	8/48 (16.7%)		2/55 (3.6%)
C-reactive protein increased	4/48 (8.3%)		2/55 (3.6%)
Electrocardiogram QT prolonged	5/48 (10.4%)		1/55 (1.8%)
Gamma-glutamyltransferase increased	3/48 (6.3%)		0/55 (0%)
Protein total decreased	3/48 (6.3%)		1/55 (1.8%)
Weight decreased	3/48 (6.3%)		5/55 (9.1%)
Metabolism and nutrition disorders
Decreased appetite	15/48 (31.3%)		15/55 (27.3%)
Dehydration	2/48 (4.2%)		4/55 (7.3%)
Hyperglycaemia	10/48 (20.8%)		6/55 (10.9%)
Hyperkalaemia	0/48 (0%)		3/55 (5.5%)
Hypoalbuminaemia	1/48 (2.1%)		3/55 (5.5%)
Hypocalcaemia	2/48 (4.2%)		4/55 (7.3%)
Hypokalaemia	8/48 (16.7%)		13/55 (23.6%)
Hyponatraemia	3/48 (6.3%)		2/55 (3.6%)
Hypophosphataemia	5/48 (10.4%)		4/55 (7.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/48 (12.5%)		3/55 (5.5%)
Back pain	7/48 (14.6%)		4/55 (7.3%)
Bone pain	1/48 (2.1%)		3/55 (5.5%)
Musculoskeletal pain	0/48 (0%)		4/55 (7.3%)
Myalgia	3/48 (6.3%)		1/55 (1.8%)
Neck pain	3/48 (6.3%)		1/55 (1.8%)
Pain in extremity	1/48 (2.1%)		3/55 (5.5%)
Nervous system disorders
Dizziness	3/48 (6.3%)		3/55 (5.5%)
Dysgeusia	9/48 (18.8%)		7/55 (12.7%)
Headache	7/48 (14.6%)		5/55 (9.1%)
Hypoaesthesia	10/48 (20.8%)		1/55 (1.8%)
Neuropathy peripheral	11/48 (22.9%)		6/55 (10.9%)
Peripheral sensory neuropathy	4/48 (8.3%)		2/55 (3.6%)
Psychiatric disorders
Agitation	0/48 (0%)		3/55 (5.5%)
Anxiety	3/48 (6.3%)		3/55 (5.5%)
Confusional state	3/48 (6.3%)		1/55 (1.8%)
Insomnia	12/48 (25%)		7/55 (12.7%)
Renal and urinary disorders
Haematuria	3/48 (6.3%)		3/55 (5.5%)
Pollakiuria	4/48 (8.3%)		1/55 (1.8%)
Respiratory, thoracic and mediastinal disorders
Cough	5/48 (10.4%)		11/55 (20%)
Dysphonia	5/48 (10.4%)		2/55 (3.6%)
Dyspnoea	2/48 (4.2%)		7/55 (12.7%)
Epistaxis	3/48 (6.3%)		6/55 (10.9%)
Hiccups	3/48 (6.3%)		9/55 (16.4%)
Oropharyngeal pain	3/48 (6.3%)		3/55 (5.5%)
Skin and subcutaneous tissue disorders
Alopecia	12/48 (25%)		3/55 (5.5%)
Dry skin	0/48 (0%)		3/55 (5.5%)
Erythema	0/48 (0%)		3/55 (5.5%)
Night sweats	0/48 (0%)		3/55 (5.5%)
Pruritus	2/48 (4.2%)		6/55 (10.9%)
Rash	5/48 (10.4%)		6/55 (10.9%)
Vascular disorders
Flushing	1/48 (2.1%)		4/55 (7.3%)
Hypotension	2/48 (4.2%)		4/55 (7.3%)

Limitations/Caveats

This is a preliminary study with a limited number of participants, which was performed primarily to assess safety.The sample size for this study was determined by clinical rather than statistical considerations.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.