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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01290549
• Date of registration: 03/02/2011
• Prospective Registration: Yes
• Primary sponsor: Genentech, Inc.
• Public title: 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
• Scientific title: 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
• Date of first enrolment: March 22, 2011
• Target sample size: 95
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01290549
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Canada, France, Netherlands, United States

Contacts

• Name: Yu-Waye Chu, M.D.
• Affiliation: Genentech, Inc.

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Lymphocytic Leukemia

Non-Hodgkins Lymphoma

Intervention(s)

Drug: Polatuzumab Vedotin

Drug: Rituximab

Primary Outcome(s)

Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Time Frame: Cycle 1 (Days 1-21)]

Percentage of Participants With Adverse Events (AEs) [Time Frame: Baseline up to 646 Days]

Proposed Phase II Dose of Polatuzumab Vedotin [Time Frame: Cycle 1 (Days 1-21)]

Maximum Tolerated Dose [Time Frame: Cycle 1 (Days 1-21)]

Secondary Outcome(s)

Percentage of AUCinf (AUCextrap)-Polatuzumab Vedotin Monotherapy [Time Frame: 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 [Time Frame: 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 of Rituximab When Given in Combination With Polatuzumab Vedotin [Time Frame: 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 [Time Frame: 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-Polatuzumab Vedotin Monotherapy [Time Frame: 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 [Time Frame: 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)]

Area Under the Curve (AUC) from Time 0 to The Last Quantifiable Time Point (AUClast)-Polatuzumab Vedotin Monotherapy [Time Frame: 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)]

AUCextrap of Rituximab When Given in Combination With Polatuzumab Vedotin [Time Frame: 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)]

Progression Free Survival (PFS), as Assessed by Using Modified Response Criteria for Non-Hodgkin Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL) [Time Frame: 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])]

AUCinf of Rituximab When Given in Combination With Polatuzumab Vedotin [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 Participants With Objective Response [Complete Response (CR) or Partial Response (PR)], as Assessed by Using Modified Response Criteria for NHL or CLL [Time Frame: 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)]

AUClast of Rituximab When Given in Combination With Polatuzumab Vedotin [Time Frame: 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-Polatuzumab Vedotin Combined with Rituximab [Time Frame: 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 of Rituximab When Given in Combination With Polatuzumab Vedotin [Time Frame: 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)]

Duration of Response, as Assessed by Using Modified Response Criteria for NHL or CLL [Time Frame: 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])]

Maximum Plasma Concentration (Cmax)-Polatuzumab Vedotin Monotherapy [Time Frame: 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 Participants with Best Overall Response (BOR), as Assessed by Using Modified Response Criteria for NHL or CLL [Time Frame: 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])]

AUC Extrapolating to Time of Infinity (AUCinf)-Polatuzumab Vedotin Monotherapy [Time Frame: 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 Combined with Rituximab [Time Frame: 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 [Time Frame: Preinfusion (0 hour) on Day 1 of Cycles 1, 2, 4, and at the treatment completion/early termination visit (up to 646 days)]

Secondary ID(s)

DCS4968g

GO01294

2011-002330-39

Source(s) of Monetary Support

Please refer to primary and secondary sponsors