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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

Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01290549
Collaborator
(none)
95
Enrollment
16
Locations
2
Arms
43.9
Actual Duration (Months)
5.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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
Phase 1

Study Design

Study Type:
Interventional
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 :
Mar 22, 2011
Actual Primary Completion Date :
Jun 29, 2012
Actual Study Completion Date :
Nov 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 Names:
  • 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 Names:
  • 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) [Cycle 1 (Days 1-21)]

    2. Maximum Tolerated Dose [Cycle 1 (Days 1-21)]

    3. Proposed Phase II Dose of Polatuzumab Vedotin [Cycle 1 (Days 1-21)]

    4. Percentage of Participants With Adverse Events (AEs) [Baseline up to 646 Days]

    Secondary Outcome Measures

    1. 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)]

    2. 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])]

    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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Site City State Country Postal Code
    1 Stanford Cancer Center Stanford California United States 94305-5820
    2 Stanford Cancer Institute Pharmacy Stanford California United States 94305
    3 Florida Cancer Specialists; Sarasota Sarasota Florida United States 34232
    4 Roswell Park Cancer Inst. Buffalo New York United States 14263
    5 Sarah Cannon Cancer Center Germantown Tennessee United States 38138
    6 M.D Anderson Cancer Center; Oncology Houston Texas United States 77030
    7 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109
    8 Cross Cancer Institute ; Dept of Medical Oncology Edmonton Alberta Canada T6G 1Z2
    9 British Columbia Cancer Agency Vancouver British Columbia Canada V5Z 1H6
    10 McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology Montreal Quebec Canada H3T 1E2
    11 CHU Dijon - SCE Hemato Dijon France 21000
    12 Centre Hospitalier Regional Universitaire de Lille Lille France
    13 CHU Lapeyronie, Hematologie Montpellier France 34295
    14 Centre Hospitalier Lyon Sud; Hematolgie Pierre Benite France 69495
    15 Centre Henri Becquerel; Hematologie Rouen France 76038
    16 Academisch Medisch Centrum; Hematologie Amsterdam Netherlands 1105 AZ

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT01290549
    Other Study ID Numbers:
    • DCS4968g
    • GO01294
    • 2011-002330-39
    First Posted:
    Feb 7, 2011
    Last Update Posted:
    Jun 16, 2017
    Last Verified:
    Jun 1, 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
    Rituximab

    Study Results

    No Results Posted as of Jun 16, 2017