Chronic Lymphocytic Leukemia, Non-Hodgkins Lymphoma
Conditions
Brief summary
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.
Interventions
DRUGPolatuzumab Vedotin
Participants will receive escalating intravenous dose of polatuzumab vedotin.
DRUGRituximab
Rituximab will be administered by an IV infusion at 375 mg/m\^2 body surface area dose q3w.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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) |
| 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) |
| 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) |
| 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) |
| 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]) |
Countries
Canada, France, Netherlands, United States
Outcome results
None listed