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

• ClinicalTrials.gov Identifier: NCT01290549
• Recruitment Status: Completed
• First Posted: February 7, 2011
• Last Update Posted: June 16, 2017
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: February 3, 2011
• First Posted Date: February 7, 2011
• Last Update Posted Date: June 16, 2017
• Actual Study Start Date: March 22, 2011
• Actual Primary Completion Date: June 29, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 14, 2017)

• Percentage of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Days 1-21) ]
• Maximum Tolerated Dose [ Time Frame: Cycle 1 (Days 1-21) ]
• Proposed Phase II Dose of Polatuzumab Vedotin [ Time Frame: Cycle 1 (Days 1-21) ]
• Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to 646 Days ]

Original Primary Outcome Measures (submitted: February 4, 2011)

• Incidence of dose-limiting toxicities (DLTs) [ Time Frame: 21 days ]
• Nature of dose-limiting toxicities (DLTs) [ Time Frame: 21 days ]

Current Secondary Outcome Measures (submitted: June 14, 2017)

• 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) ]
• 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]) ]
• 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) ]
• 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]) ]
• 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]) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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 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) ]
• 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) ]
• 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) ]
• 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) ]

Original Secondary Outcome Measures (submitted: February 4, 2011)

• Incidence of adverse events [ Time Frame: Up to 12 months ]
• Nature of adverse events [ Time Frame: Up to 12 months ]
• Severity of adverse events [ Time Frame: Up to 12 months ]
• Incidence of anti-therapeutic antibodies (ATAs) against DCDS4501A [ Time Frame: Up to 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• Official 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Hodgkins Lymphoma
• Chronic Lymphocytic Leukemia

Intervention

• Drug: Polatuzumab Vedotin
  Participants will receive escalating intravenous dose of polatuzumab vedotin.
  Other Name: DCDS4501A
• Drug: Rituximab
  Rituximab will be administered by an IV infusion at 375 mg/m^2 body surface area dose q3w.

Study Arms

• Experimental: Polatuzumab Vedotin
  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).
  Intervention: Drug: Polatuzumab Vedotin
• Experimental: Polatuzumab Vedotin + Rituximab
  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.
  Interventions:

  • Drug: Polatuzumab Vedotin
  • Drug: Rituximab

Publications *

• Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.
• Lu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.
• Palanca-Wessels MC, Czuczman M, Salles G, Assouline S, Sehn LH, Flinn I, Patel MR, Sangha R, Hagenbeek A, Advani R, Tilly H, Casasnovas O, Press OW, Yalamanchili S, Kahn R, Dere RC, Lu D, Jones S, Jones C, Chu YW, Morschhauser F. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet Oncol. 2015 Jun;16(6):704-15. doi: 10.1016/S1470-2045(15)70128-2. Epub 2015 Apr 27.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 8, 2013): 95
• Original Estimated Enrollment (submitted: February 4, 2011): 99
• Actual Study Completion Date: November 18, 2014
• Actual Primary Completion Date: June 29, 2012 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, France, Netherlands, United States

Administrative Information

• NCT Number: NCT01290549
• Other Study ID Numbers: DCS4968g; GO01294 ( Other Identifier: Hoffmann-La Roche ); 2011-002330-39 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Disclosures Group, Genentech, Inc.
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Yu-Waye Chu, M.D.; Genentech, Inc.

• PRS Account: Genentech, Inc.
• Verification Date: June 2017