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.

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.

Condition or disease	Intervention/treatment	Phase
Non-Hodgkins Lymphoma; Chronic Lymphocytic Leukemia	Drug: Polatuzumab Vedotin; Drug: Rituximab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 95 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 22, 2011
• Actual Primary Completion Date: June 29, 2012
• Actual Study Completion Date: November 18, 2014

Arms and Interventions

Arm	Intervention/treatment
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).	Drug: Polatuzumab Vedotin; Participants will receive escalating intravenous dose of polatuzumab vedotin.; Other Name: DCDS4501A
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.	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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. 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) ]
2. 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]) ]
3. 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) ]
4. 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]) ]
5. 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]) ]
6. 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) ]
7. 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) ]
8. 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) ]
9. 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) ]
10. 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) ]
11. 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) ]
12. 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) ]
13. 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) ]
14. 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) ]
15. 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) ]
16. 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) ]
17. 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) ]
18. 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) ]
19. 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) ]
20. 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) ]
21. 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) ]
22. 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) ]
23. 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) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Stanford Cancer Center

Stanford, California, United States, 94305-5820

Stanford Cancer Institute Pharmacy

Stanford, California, United States, 94305

United States, Florida

Florida Cancer Specialists; Sarasota

Sarasota, Florida, United States, 34232

United States, New York

Roswell Park Cancer Inst.

Buffalo, New York, United States, 14263

United States, Tennessee

Sarah Cannon Cancer Center

Germantown, Tennessee, United States, 38138

United States, Texas

M.D Anderson Cancer Center; Oncology

Houston, Texas, United States, 77030

United States, Washington

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109

Canada, Alberta

Cross Cancer Institute ; Dept of Medical Oncology

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

British Columbia Cancer Agency

Vancouver, British Columbia, Canada, V5Z 1H6

Canada, Quebec

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, Canada, H3T 1E2

France

CHU Dijon - SCE Hemato

Dijon, France, 21000

Centre Hospitalier Regional Universitaire de Lille

Lille, France

CHU Lapeyronie, Hematologie

Montpellier, France, 34295

Centre Hospitalier Lyon Sud; Hematolgie

Pierre Benite, France, 69495

Centre Henri Becquerel; Hematologie

Rouen, France, 76038

Netherlands

Academisch Medisch Centrum; Hematologie

Amsterdam, Netherlands, 1105 AZ

Sponsors and Collaborators

Genentech, Inc.

Investigators

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

More Information

Additional Information:

Link to the publication 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT01290549
• Other Study ID Numbers: DCS4968g; GO01294 ( Other Identifier: Hoffmann-La Roche ); 2011-002330-39 ( EudraCT Number )
• First Posted: February 7, 2011
• Last Update Posted: June 16, 2017
• Last Verified: June 2017

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

Additional relevant MeSH terms:

Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Rituximab; Polatuzumab vedotin; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Immunoconjugates