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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01290549
• Other study ID #: DCS4968g
• Secondary ID: GO012942011-0023
• Status: Completed
• Phase: Phase 1
• First received: February 3, 2011
• Last updated: June 14, 2017
• Start date: March 22, 2011
• Est. completion date: November 18, 2014

Study information

• Verified date: June 2017
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: November 18, 2014
• Est. primary completion date: June 29, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkins Lymphoma

Intervention

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

Locations

Country	Name	City	State
Canada	Cross Cancer Institute ; Dept of Medical Oncology	Edmonton	Alberta
Canada	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
France	CHU Dijon - SCE Hemato	Dijon
France	Centre Hospitalier Regional Universitaire de Lille	Lille
France	CHU Lapeyronie, Hematologie	Montpellier
France	Centre Hospitalier Lyon Sud; Hematolgie	Pierre Benite
France	Centre Henri Becquerel; Hematologie	Rouen
Netherlands	Academisch Medisch Centrum; Hematologie	Amsterdam
United States	Roswell Park Cancer Inst.	Buffalo	New York
United States	Sarah Cannon Cancer Center	Germantown	Tennessee
United States	M.D Anderson Cancer Center; Oncology	Houston	Texas
United States	Florida Cancer Specialists; Sarasota	Sarasota	Florida
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford Cancer Center	Stanford	California
United States	Stanford Cancer Institute Pharmacy	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose-Limiting Toxicities (DLTs)		Cycle 1 (Days 1-21)
Primary	Maximum Tolerated Dose		Cycle 1 (Days 1-21)
Primary	Proposed Phase II Dose of Polatuzumab Vedotin		Cycle 1 (Days 1-21)
Primary	Percentage of Participants With Adverse Events (AEs)		Baseline up to 646 Days
Secondary	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)
Secondary	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])
Secondary	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)
Secondary	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])
Secondary	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])
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

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