Back to resultsA 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
Primary Purpose
Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Polatuzumab Vedotin
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkins Lymphoma
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
Sites / Locations
- Stanford Cancer Center
- Stanford Cancer Institute Pharmacy
- Florida Cancer Specialists; Sarasota
- Roswell Park Cancer Inst.
- Sarah Cannon Cancer Center
- M.D Anderson Cancer Center; Oncology
- Fred Hutchinson Cancer Research Center
- Cross Cancer Institute ; Dept of Medical Oncology
- British Columbia Cancer Agency
- McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
- CHU Dijon - SCE Hemato
- Centre Hospitalier Regional Universitaire de Lille
- CHU Lapeyronie, Hematologie
- Centre Hospitalier Lyon Sud; Hematolgie
- Centre Henri Becquerel; Hematologie
- Academisch Medisch Centrum; Hematologie
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Polatuzumab Vedotin
Polatuzumab Vedotin + Rituximab
Arm Description
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).
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Maximum Tolerated Dose
Proposed Phase II Dose of Polatuzumab Vedotin
Percentage of Participants With Adverse Events (AEs)
Secondary Outcome Measures
Percentage of Paticipants with Anti Therapeutic Antibodies (ATAs) Against Polatuzumab Vedotin
Progression Free Survival (PFS), as Assessed by Using Modified Response Criteria for Non-Hodgkin Lymphoma (NHL) or Chronic Lymphocytic Leukemia (CLL)
Percentage of Participants With Objective Response [Complete Response (CR) or Partial Response (PR)], as Assessed by Using Modified Response Criteria for NHL or CLL
Duration of Response, as Assessed by Using Modified Response Criteria for NHL or CLL
Percentage of Participants with Best Overall Response (BOR), as Assessed by Using Modified Response Criteria for NHL or CLL
Area Under the Curve (AUC) from Time 0 to The Last Quantifiable Time Point (AUClast)-Polatuzumab Vedotin Monotherapy
AUC Extrapolating to Time of Infinity (AUCinf)-Polatuzumab Vedotin Monotherapy
Percentage of AUCinf (AUCextrap)-Polatuzumab Vedotin Monotherapy
Maximum Plasma Concentration (Cmax)-Polatuzumab Vedotin Monotherapy
Clearance-Polatuzumab Vedotin Monotherapy
Volume of Distribution at Steady State-Polatuzumab Vedotin Monotherapy
AUClast - Polatuzumab Vedotin Combined with Rituximab
AUCinf-Polatuzumab Vedotin Combined with Rituximab
AUCextrap-Polatuzumab Vedotin Combined with Rituximab
Cmax-Polatuzumab Vedotin Combined with Rituximab
Clearance-Polatuzumab Vedotin Combined with Rituximab
Volume of Distribution at Steady State-Polatuzumab Vedotin Combined with Rituximab
AUClast of Rituximab When Given in Combination With Polatuzumab Vedotin
AUCinf of Rituximab When Given in Combination With Polatuzumab Vedotin
AUCextrap of Rituximab When Given in Combination With Polatuzumab Vedotin
Cmax of Rituximab When Given in Combination With Polatuzumab Vedotin
Clearance of Rituximab When Given in Combination With Polatuzumab Vedotin
Volume of Distribution at Steady State-of Rituximab When Given in Combination With Polatuzumab Vedotin
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01290549
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
March 22, 2011 (Actual)
Primary Completion Date
June 29, 2012 (Actual)
Study Completion Date
November 18, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
95 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Polatuzumab Vedotin
Arm Type
Experimental
Arm Description
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).
Arm Title
Polatuzumab Vedotin + Rituximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Polatuzumab Vedotin
Other Intervention Name(s)
DCDS4501A
Intervention Description
Participants will receive escalating intravenous dose of polatuzumab vedotin.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab will be administered by an IV infusion at 375 mg/m^2 body surface area dose q3w.
Primary Outcome Measure Information:
Title
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time Frame
Cycle 1 (Days 1-21)
Title
Maximum Tolerated Dose
Time Frame
Cycle 1 (Days 1-21)
Title
Proposed Phase II Dose of Polatuzumab Vedotin
Time Frame
Cycle 1 (Days 1-21)
Title
Percentage of Participants With Adverse Events (AEs)
Time Frame
Baseline up to 646 Days
Secondary Outcome Measure Information:
Title
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)
Title
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])
Title
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)
Title
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])
Title
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])
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yu-Waye Chu, M.D.
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5820
Country
United States
Facility Name
Stanford Cancer Institute Pharmacy
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Florida Cancer Specialists; Sarasota
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Roswell Park Cancer Inst.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Sarah Cannon Cancer Center
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
M.D Anderson Cancer Center; Oncology
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Cross Cancer Institute ; Dept of Medical Oncology
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
British Columbia Cancer Agency
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1H6
Country
Canada
Facility Name
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
CHU Dijon - SCE Hemato
City
Dijon
ZIP/Postal Code
21000
Country
France
Facility Name
Centre Hospitalier Regional Universitaire de Lille
City
Lille
Country
France
Facility Name
CHU Lapeyronie, Hematologie
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Centre Hospitalier Lyon Sud; Hematolgie
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Centre Henri Becquerel; Hematologie
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Academisch Medisch Centrum; Hematologie
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
32770353
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.
Results Reference
derived
PubMed Identifier
32705923
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.
Results Reference
derived
PubMed Identifier
25925619
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.
Results Reference
derived
Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/25925619?dopt=Abstract
Description
Link to the publication
Learn more about this trial
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
We'll reach out to this number within 24 hrs