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A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma

NCT02257567

Description:

This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18 weeks for participants with DLBCL and 24 weeks for participants with FL.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
  • Official Title: A PHASE IB/II STUDY EVALUATING THE SAFETY, TOLERABILITY AND ANTI-TUMOR ACTIVITY OF POLATUZUMAB VEDOTIN (DCDS4501A) IN COMBINATION WITH RITUXIMAB (R) OR OBINUTUZUMAB (G) PLUS BENDAMUSTINE (B) IN RELAPSED OR REFRACTORY FOLLICULAR OR DIFFUSE LARGE B-CELL LYMPHOMA

Clinical Trial IDs

  • ORG STUDY ID: GO29365
  • SECONDARY ID: 2014-001361-28
  • NCT ID: NCT02257567

Conditions

  • Lymphoma

Interventions

DrugSynonymsArms
BendamustineTreanda; Ribomustin; LevactArm A (Phase II Randomization): Polatuzumab+BR in FL
ObinutuzumabGA101; Gazyva; GazyvaroArm E (Phase II Expansion): Polatuzumab+BG in FL
Polatuzumab vedotinDCDS4501AArm A (Phase II Randomization): Polatuzumab+BR in FL
RituximabRituxan; MabTheraArm A (Phase II Randomization): Polatuzumab+BR in FL

Purpose

This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18 weeks for participants with DLBCL and 24 weeks for participants with FL.

Trial Arms

NameTypeDescriptionInterventions
Arm A (Phase II Randomization): Polatuzumab+BR in FLExperimentalPolatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL.
  • Bendamustine
  • Polatuzumab vedotin
  • Rituximab
Arm B (Phase II Randomization): BR in FLActive ComparatorBendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL.
  • Bendamustine
  • Rituximab
Arm C (Phase II Randomization): Polatuzumab+BR in DLBCLExperimentalPolatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL.
  • Bendamustine
  • Polatuzumab vedotin
  • Rituximab
Arm D (Phase II Randomization): BR in DLBCLActive ComparatorBendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL.
  • Bendamustine
  • Rituximab
Arm E (Phase II Expansion): Polatuzumab+BG in FLExperimentalPolatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL.
  • Bendamustine
  • Obinutuzumab
  • Polatuzumab vedotin
Arm F (Phase II Expansion): Polatuzumab+BG in DLBCLExperimentalPolatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL.
  • Bendamustine
  • Obinutuzumab
  • Polatuzumab vedotin
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCLExperimentalPolatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL for up to 6 cycles.
  • Bendamustine
  • Polatuzumab vedotin
  • Rituximab
Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FLExperimentalPolatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL for up to 6 cycles.
  • Bendamustine
  • Polatuzumab vedotin
  • Rituximab
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCLExperimentalPolatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL for up to 6 cycles.
  • Bendamustine
  • Obinutuzumab
  • Polatuzumab vedotin
Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FLExperimentalPolatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL for up to 6 cycles.
  • Bendamustine
  • Obinutuzumab
  • Polatuzumab vedotin

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed
             or refractory DLBCL

          -  If the participant has received prior bendamustine, response duration must have been
             greater than (>) 1 year (for participants who have relapse disease after a prior
             regimen)

          -  At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5
             centimeters (cm) in its longest dimension

          -  Confirmed availability of archival or freshly collected tumor tissue

          -  Life expectancy of at least 24 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Adequate hematological function unless inadequate function is due to underlying
             disease

        Exclusion Criteria:

          -  History of severe allergic or anaphylactic reactions to humanized or murine
             monoclonal antibodies (MAbs, or recombinant antibody-related fusion proteins) or
             known sensitivity or allergy to murine products

          -  Contraindication to bendamustine, rituximab, or obinutuzumab

          -  Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4
             weeks or 5 half-lives before Cycle 1 Day 1

          -  Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy,
             or any investigational agent for the purposes of treating cancer within 2 weeks prior
             to Cycle 1 Day 1

          -  Ongoing corticosteroid use >30 mg per day prednisone or equivalent, for purposes
             other than lymphoma symptom control

          -  Completion of autologous stem cell transplant (SCT) within 100 days prior to Cycle 1
             Day 1

          -  Prior allogeneic SCT

          -  Eligibility for autologous SCT

          -  Grade 3b FL

          -  History of transformation of indolent disease to DLBCL

          -  Primary or secondary CNS lymphoma

          -  Current Grade >1 peripheral neuropathy

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results, including significant
             cardiovascular disease (such as New York Heart Association Class III or IV cardiac
             disease, myocardial infarction within the last 6 months, unstable arrhythmias, or
             unstable angina) or significant pulmonary disease (including obstructive pulmonary
             disease and history of bronchospasm)

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
             (excluding fungal infections of nail beds) at study enrollment or any major episode
             of infection requiring treatment with IV antibiotics or hospitalization within 4
             weeks prior to Cycle 1 Day 1

          -  Suspected or latent tuberculosis

          -  Positive test results for chronic hepatitis B virus (HBV) infection or for hepatitis
             C virus (HCV) antibody

          -  Known history of human immunodeficiency virus (HIV) seropositive status or known
             infection with human T-cell leukemia virus 1 (HTLV-1) virus

          -  Women who are pregnant or lactating or who intend to become pregnant within a year of
             the last dose of study treatment in the rituximab cohort or within 18 months of last
             dose in the obinutuzumab cohort

          -  Evidence of laboratory abnormalities in standard renal, hepatic, or coagulation
             function tests
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Percentage of Participants with Adverse Events
Time Frame:From Baseline until up to 90 days after last dose (up to 36 weeks overall)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Obinutuzumab in Arms E and F (mg/mL)
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4 and Day 2 of Cycle 1; at EOI on Day 2 of Cycle 1 and Day 1 of Cycles 1, 4; post-dose (1, 2, 3, 4 h) Day 2 of Cycle 1; after last dose (24 weeks); randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Pharmacokinetics: Cmax of Bendamustine and Rituximab in Arms B and D (mg/mL)
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4 and Day 2 of Cycle 1; at EOI on Days 1, 2 of Cycle 1; post-dose (1, 2, 3, 4 h) on Day 2 of Cycle 1 (up to 3 months overall)
Safety Issue:
Description:
Measure:Percentage of Participants with CR or PR According to Modified Lugano Criteria as Measured by CT Scan and Determined by IRC and Investigator
Time Frame:6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)
Safety Issue:
Description:
Measure:Percentage of Participants by Best Objective Response (BOR) According to Modified Lugano Criteria as Measured by PET Scan or CT Scan and Determined by the Investigator
Time Frame:Baseline, Cycle 3 Day 15, and 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days); then every 3 months for 2 years; thereafter every 6 months until progression or withdrawal (up to about 4.5 years overall)
Safety Issue:
Description:
Measure:Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS)
Time Frame:Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall)
Safety Issue:
Description:
Measure:Pharmacokinetics: Area Under Concentration-Time Curve (AUC) of Polatuzumab, Bendamustine, and Rituximab in Cohort 1A (h*mg/mL)
Time Frame:Pre-dose (0 to 4 h) and end of infusion (EOI) on Day 2 of Cycle 1 and Day 1 of Cycles 2, 4; on Days 8, 15 of Cycle 1; randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Obinutuzumab in Cohort 1B (h*mg/mL)
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycle 1, 2, 4 and Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; at EOI on Day 2 of Cycle 1 and Day 1 of Cycles 2, 4; randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Rituximab in Arms A and C (h*mg/mL)
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4; at EOI on Day 2 of Cycle 1 and Day 1 of Cycles 1, 4; post-dose (1, 2, 3, 4 h) on Day 2 of Cycle 1; after last dose (24 weeks); randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Pharmacokinetics: AUC of Bendamustine and Rituximab in Arms B and D (h*mg/mL)
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4 and Day 2 of Cycle 1; at EOI on Days 1, 2 of Cycle 1; post-dose (1, 2, 3, 4 h) on Day 2 of Cycle 1 (up to 3 months overall)
Safety Issue:
Description:
Measure:Pharmacokinetics: AUC of Polatuzumab, Bendamustine, and Obinutuzumab in Arms E and F (h*mg/mL)
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4 and Day 2 of Cycle 1; at EOI on Day 2 of Cycle 1 and Day 1 of Cycles 1, 4; post-dose (1, 2, 3, 4 h) Day 2 of Cycle 1; after last dose (24 weeks); randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Pharmacokinetics: Maximum Concentration (Cmax) of Polatuzumab, Bendamustine, and Rituximab in Cohort 1A (mg/mL)
Time Frame:Pre-dose (0 to 4 h) and EOI on Day 2 of Cycle 1 and Day 1 of Cycles 2, 4; on Days 8, 15 of Cycle 1; randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Obinutuzumab in Cohort 1B (mg/mL)
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycle 1, 2, 4 and Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; at EOI on Day 2 of Cycle 1 and Day 1 of Cycles 2, 4; randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Pharmacokinetics: Cmax of Polatuzumab, Bendamustine, and Rituximab in Arms A and C (mg/mL)
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4; at EOI on Day 2 of Cycle 1 and Day 1 of Cycles 1, 4; post-dose (1, 2, 3, 4 h) on Day 2 of Cycle 1; after last dose (24 weeks); randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants with Adverse Events
Time Frame:From Baseline until up to 90 days after last dose (up to 36 weeks overall)
Safety Issue:
Description:
Measure:Phase I: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Polatuzumab in Cohort 1A
Time Frame:Pre-dose (0 to 4 hours [h]) on Day 2 of Cycle 1; pre-dose (0 to 4 h) on Day 1 of Cycles 2 and 4; randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Phase I: Percentage of Participants with ATAs to Polatuzumab and Obinutuzumab in Cohort 1B
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4; pre-dose (0 to 4 h) on Day 2 of Cycle 1; randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants with ATAs to Polatuzumab in Arms A and C
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycles 2, 4; pre-dose (0 to 4 h) on Day 2 of Cycle 1; up to 30 days after last dose (approximately 28 weeks); randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Phase II: Percentage of Participants with ATAs to Polatuzumab and Obinutuzumab in Arms E and F
Time Frame:Pre-dose (0 to 4 h) on Day 1 of Cycles 1, 2, 4; pre-dose (0 to 4 h) on Day 2 of Cycle 1; up to 30 days after last dose (approximately 28 weeks); randomly during post-treatment period (up to 2 years overall)
Safety Issue:
Description:
Measure:Percentage of Participants with CR According to Modified Lugano Criteria as Measured by PET Scan and Determined by the Investigator
Time Frame:6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)
Safety Issue:
Description:
Measure:Percentage of Participants with CR According to Modified Lugano Criteria as Measured by CT Scan and Determined by IRC and Investigator
Time Frame:6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)
Safety Issue:
Description:
Measure:Percentage of Participants with CR or Partial Response (PR) According to Modified Lugano Criteria as Measured by PET Scan and Determined by IRC and Investigator
Time Frame:6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 or 28 days) or last dose of study drug (up to 28 weeks overall)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

November 1, 2016