A Study of Escalating Doses of Polatuzumab Vedotin in Participants With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukemia and Polatuzumab Vedotin in Combination With Rituximab in Participants With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma

Study Overview
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Brief Summary
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This is a Phase I, multicenter, open-label, dose-escalation study of polatuzumab vedotin administered as a single agent by intravenous (IV) infusion to participants with relapsed or refractory hematologic malignancies. In Phase Ib, participants will receive polatuzumab vedotin in combination with rituximab.

Official Title
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An Open-Label, Multicenter, Phase I Trial of the Safety and Pharmacokinetics Of Escalating Doses of DCDS4501A in Patients With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukemia and DCDS4501A in Combination With Rituximab in Patients With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma

Conditions
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Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Polatuzumab Vedotin
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Life expectancy of at least 12 weeks History of one of the following histologically-documented hematologic malignancy for which no effective standard therapy exists: indolent non Hodgkin's lymphoma (NHL), Grade 3b follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) All participants (NHL and B-cell chronic lymphocytic leukemia [B-CLL]) must have at least one bi-dimensionally measurable lesion For all men or women of childbearing potential (unless surgically sterile): use of adequate methods of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly Exclusion Criteria: Prior use of any monoclonal antibody or antibody-drug conjugate within 4 weeks before Cycle 1, Day 1 Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent within 2 weeks prior to Cycle 1, Day 1. Adverse events from any previous treatments must be resolved or stabilized prior to Cycle 1, Day 1, except for neuropathy Completion of autologous stem cell transplant within 100 days prior to Cycle 1, Day 1 Prior allogeneic stem cell transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polatuzumab Vedotin<br>Polatuzumab vedotin will be administered by an IV infusion of escalating doses (starting dose of 0.1 mg/kg, potentially to be followed by 0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, and 4.0 mg/kg doses) every 3 weeks (q3w) (Day 1 of each 21 day cycle). | Drug: Polatuzumab Vedotin<br>* Participants will receive escalating intravenous dose of polatuzumab vedotin.<br>* Other names: DCDS4501A;|
| Experimental: Polatuzumab Vedotin + Rituximab<br>Polatuzumab vedotin will be administered by an IV infusion q3w (Day 1 of each 21 day cycle). Rituximab was administered by an IV infusion at 375 milligrams per square meter (mg/m^2) body surface area dose q3w. | Drug: Polatuzumab Vedotin<br>* Participants will receive escalating intravenous dose of polatuzumab vedotin.<br>* Other names: DCDS4501A;Drug: Rituximab<br>* Rituximab will be administered by an IV infusion at 375 mg/m^2 body surface area dose q3w.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) |  | Cycle 1 (Days 1-21) | 
| Maximum Tolerated Dose |  | Cycle 1 (Days 1-21) | 
| Proposed Phase II Dose of Polatuzumab Vedotin |  | Cycle 1 (Days 1-21) | 
| Percentage of Participants With Adverse Events (AEs) |  | Baseline up to 646 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Paticipants with Anti Therapeutic Antibodies (ATAs) Against Polatuzumab Vedotin |  | Preinfusion (0 hour) on Day 1 of Cycles 1, 2, 4, and at the treatment completion/early termination visit (up to 646 days) | 
| Progression Free Survival (PFS), as Assessed by Using Modified Response Criteria for Non-Hodgkin Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL) |  | Baseline up to disease progression or death (Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug [up to 44.5 months]) | 
| Percentage of Participants With Objective Response [Complete Response (CR) or Partial Response (PR)], as Assessed by Using Modified Response Criteria for NHL or CLL |  | Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug (up to 44.5 months) | 
| Duration of Response, as Assessed by Using Modified Response Criteria for NHL or CLL |  | Baseline up to disease progression or death (Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug [up to 44.5 months]) | 
| Percentage of Participants with Best Overall Response (BOR), as Assessed by Using Modified Response Criteria for NHL or CLL |  | Baseline up to disease progression or death (Every 3 months while on study treatment from the initiation of therapy and 30 days after last dose of study drug [up to 44.5 months]) | 
| Area Under the Curve (AUC) from Time 0 to The Last Quantifiable Time Point (AUClast)-Polatuzumab Vedotin Monotherapy |  | Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| AUC Extrapolating to Time of Infinity (AUCinf)-Polatuzumab Vedotin Monotherapy |  | Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| Percentage of AUCinf (AUCextrap)-Polatuzumab Vedotin Monotherapy |  | Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| Maximum Plasma Concentration (Cmax)-Polatuzumab Vedotin Monotherapy |  | Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| Clearance-Polatuzumab Vedotin Monotherapy |  | Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| Volume of Distribution at Steady State-Polatuzumab Vedotin Monotherapy |  | Pre infusion (0 hour) and 0.5, 4 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| AUClast - Polatuzumab Vedotin Combined with Rituximab |  | Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| AUCinf-Polatuzumab Vedotin Combined with Rituximab |  | Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| AUCextrap-Polatuzumab Vedotin Combined with Rituximab |  | Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| Cmax-Polatuzumab Vedotin Combined with Rituximab |  | Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| Clearance-Polatuzumab Vedotin Combined with Rituximab |  | Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| Volume of Distribution at Steady State-Polatuzumab Vedotin Combined with Rituximab |  | Pre infusion (0 hour) and 0.5 hours post infusion (duration of infusion: 90 minutes for first infusion and 30 minutes for subsequent infusions) on Cycle 1 Day 1; Cycle 1 Days 2, 4, 8, 11 and 15 (cycle length: 21 days) | 
| AUClast of Rituximab When Given in Combination With Polatuzumab Vedotin |  | Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days) | 
| AUCinf of Rituximab When Given in Combination With Polatuzumab Vedotin |  | Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days) | 
| AUCextrap of Rituximab When Given in Combination With Polatuzumab Vedotin |  | Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days) | 
| Cmax of Rituximab When Given in Combination With Polatuzumab Vedotin |  | Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days) | 
| Clearance of Rituximab When Given in Combination With Polatuzumab Vedotin |  | Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days) | 
| Volume of Distribution at Steady State-of Rituximab When Given in Combination With Polatuzumab Vedotin |  | Pre rituximab (0 hour) dose and 30 minutes post rituximab dose on Cycle 1 Day 1; Cycle 1 Days 4, 8, 15 (cycle length: 21 days) |