Clinical trial NCT01290549: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Hodgkins Lymphoma
Chronic Lymphocytic Leukemia
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-02-07
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (Days 1-21)
measure: Maximum Tolerated Dose
timeFrame: Cycle 1 (Days 1-21)
measure: Proposed Phase II Dose of Polatuzumab Vedotin
timeFrame: Cycle 1 (Days 1-21)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to 646 Days
Secondary outcomes:
measure: Percentage of Paticipants with Anti Therapeutic Antibodies (ATAs) Against Polatuzumab Vedotin
timeFrame: Preinfusion (0 hour) on Day 1 of Cycles 1, 2, 4, and at the treatment completion/early termination visit (up to 646 days)
measure: Progression Free Survival (PFS), as Assessed by Using Modified Response Criteria for Non-Hodgkin Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL)
timeFrame: 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])
measure: Percentage of Participants With Objective Response [Complete Response (CR) or Partial Response (PR)], as Assessed by Using Modified Response Criteria for NHL or CLL
timeFrame: 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)
measure: Duration of Response, as Assessed by Using Modified Response Criteria for NHL or CLL
timeFrame: 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])
measure: Percentage of Participants with Best Overall Response (BOR), as Assessed by Using Modified Response Criteria for NHL or CLL
timeFrame: 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])
measure: Area Under the Curve (AUC) from Time 0 to The Last Quantifiable Time Point (AUClast)-Polatuzumab Vedotin Monotherapy
timeFrame: 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)
measure: AUC Extrapolating to Time of Infinity (AUCinf)-Polatuzumab Vedotin Monotherapy
timeFrame: 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)
measure: Percentage of AUCinf (AUCextrap)-Polatuzumab Vedotin Monotherapy
timeFrame: 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)
measure: Maximum Plasma Concentration (Cmax)-Polatuzumab Vedotin Monotherapy
timeFrame: 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)
measure: Clearance-Polatuzumab Vedotin Monotherapy
timeFrame: 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)
measure: Volume of Distribution at Steady State-Polatuzumab Vedotin Monotherapy
timeFrame: 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)
measure: AUClast - Polatuzumab Vedotin Combined with Rituximab
timeFrame: 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)
measure: AUCinf-Polatuzumab Vedotin Combined with Rituximab
timeFrame: 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)
measure: AUCextrap-Polatuzumab Vedotin Combined with Rituximab
timeFrame: 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)
measure: Cmax-Polatuzumab Vedotin Combined with Rituximab
timeFrame: 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)
measure: Clearance-Polatuzumab Vedotin Combined with Rituximab
timeFrame: 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)
measure: Volume of Distribution at Steady State-Polatuzumab Vedotin Combined with Rituximab
timeFrame: 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)
measure: AUClast of Rituximab When Given in Combination With Polatuzumab Vedotin
timeFrame: 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)
measure: AUCinf of Rituximab When Given in Combination With Polatuzumab Vedotin
timeFrame: 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)
measure: AUCextrap of Rituximab When Given in Combination With Polatuzumab Vedotin
timeFrame: 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)
measure: Cmax of Rituximab When Given in Combination With Polatuzumab Vedotin
timeFrame: 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)
measure: Clearance of Rituximab When Given in Combination With Polatuzumab Vedotin
timeFrame: 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)
measure: Volume of Distribution at Steady State-of Rituximab When Given in Combination With Polatuzumab Vedotin
timeFrame: 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)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute Pharmacy
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists; Sarasota
state: Florida
city: Buffalo
country: United States
facility: Roswell Park Cancer Inst.
state: New York
city: Germantown
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Houston
country: United States
facility: M.D Anderson Cancer Center; Oncology
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Edmonton
country: Canada
facility: Cross Cancer Institute ; Dept of Medical Oncology
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Montreal
country: Canada
facility: McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
state: Quebec
city: Dijon
country: France
facility: CHU Dijon - SCE Hemato
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille
city: Montpellier
country: France
facility: CHU Lapeyronie, Hematologie
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud; Hematolgie
city: Rouen
country: France
facility: Centre Henri Becquerel; Hematologie
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum; Hematologie
Study officials:
affiliation: Genentech, Inc.
name: Yu-Waye Chu, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.