ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Obinutuzumab, Rituximab, Polatuzumab Vedotin, and Venetoclax in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02611323
Recruitment Status : Recruiting
First Posted : November 20, 2015
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and venetoclax in participants with relapsed or refractory FL, and with rituximab, polatuzumab vedotin, and venetoclax in participants with DLBCL. Participants with FL who achieve complete response (CR), partial response (PR), or stable disease (SD) at the end of induction therapy will receive post-induction treatment with obinutuzumab and venetoclax, and participants with DLBCL who achieve CR or PR at the end of induction (EOI) will receive post-induction treatment with rituximab and venetoclax.

Condition or disease Intervention/treatment Phase
Non-Hodgkin's Lymphoma Drug: Obinutuzumab Drug: Rituximab Drug: Polatuzumab Vedotin Drug: Venetoclax Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 134 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Polatuzumab Vedotin and Venetoclax in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Venetoclax in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Actual Study Start Date : March 9, 2016
Estimated Primary Completion Date : December 9, 2021
Estimated Study Completion Date : December 9, 2021


Arm Intervention/treatment
Experimental: Dose-Escalation Cohort: FL
Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and venetoclax when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Drug: Obinutuzumab
Participants will receive a fixed dose of obinutuzumab, 1000 mg via intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 1000 mg via IV infusion on Day 1 of every other month (starting from Month 2) for up to 24 months, until disease progression or unacceptable toxicity.

Drug: Polatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) (for FL), and 1.8 mg/kg (for DLBCL) on Day 1 of each 21-day cycle for up to 18 weeks during induction treatment. Polatuzumab vedotin will not be given during the post-induction period.

Drug: Venetoclax
Participants will receive venetoclax film-coated tablets at doses of 200, 400, 600, or 800 mg (for FL), and 400, 600, or 800 mg (for DLBCL) on Days 1 to 21 of each 21-day cycle. Post-induction venetoclax may continue for up to 8 months, until disease progression or unacceptable toxicity.

Experimental: Dose-Escalation Cohort: DLBCL
Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at escalating doses to identify the RP2D of venetoclax when combined with fixed doses of polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
Drug: Rituximab
Participants will receive a fixed dose of rituximab, 375 milligrams per square meter (mg/m^2) via IV infusion to be given on Day 1 of Cycles 1 to 6. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month (starting from Month 2) for up to 8 months, until disease progression or unacceptable toxicity.

Drug: Polatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) (for FL), and 1.8 mg/kg (for DLBCL) on Day 1 of each 21-day cycle for up to 18 weeks during induction treatment. Polatuzumab vedotin will not be given during the post-induction period.

Drug: Venetoclax
Participants will receive venetoclax film-coated tablets at doses of 200, 400, 600, or 800 mg (for FL), and 400, 600, or 800 mg (for DLBCL) on Days 1 to 21 of each 21-day cycle. Post-induction venetoclax may continue for up to 8 months, until disease progression or unacceptable toxicity.

Experimental: Expansion Cohort: FL
Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at the RP2D identified during the dose-escalation phase, in addition to obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Drug: Obinutuzumab
Participants will receive a fixed dose of obinutuzumab, 1000 mg via intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 1000 mg via IV infusion on Day 1 of every other month (starting from Month 2) for up to 24 months, until disease progression or unacceptable toxicity.

Drug: Polatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) (for FL), and 1.8 mg/kg (for DLBCL) on Day 1 of each 21-day cycle for up to 18 weeks during induction treatment. Polatuzumab vedotin will not be given during the post-induction period.

Drug: Venetoclax
Participants will receive venetoclax film-coated tablets at doses of 200, 400, 600, or 800 mg (for FL), and 400, 600, or 800 mg (for DLBCL) on Days 1 to 21 of each 21-day cycle. Post-induction venetoclax may continue for up to 8 months, until disease progression or unacceptable toxicity.

Experimental: Expansion Cohort: DLBCL
Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at the RP2D identified during the dose-escalation phase, in addition to polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
Drug: Rituximab
Participants will receive a fixed dose of rituximab, 375 milligrams per square meter (mg/m^2) via IV infusion to be given on Day 1 of Cycles 1 to 6. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month (starting from Month 2) for up to 8 months, until disease progression or unacceptable toxicity.

Drug: Polatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) (for FL), and 1.8 mg/kg (for DLBCL) on Day 1 of each 21-day cycle for up to 18 weeks during induction treatment. Polatuzumab vedotin will not be given during the post-induction period.

Drug: Venetoclax
Participants will receive venetoclax film-coated tablets at doses of 200, 400, 600, or 800 mg (for FL), and 400, 600, or 800 mg (for DLBCL) on Days 1 to 21 of each 21-day cycle. Post-induction venetoclax may continue for up to 8 months, until disease progression or unacceptable toxicity.




Primary Outcome Measures :
  1. Percentage of Participants with CR, Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days) ]

Secondary Outcome Measures :
  1. Percentage of Participants with CR, Determined by the Investigator on the basis of PET and CT Scans [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days) ]
  2. Percentage of Participants with CR, Determined by the Investigator on the Basis of CT Scans Alone [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days) ]
  3. Percentage of Participants with CR, Determined by the IRC on the Basis of CT Scans Alone [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days) ]
  4. Percentage of Participants with Objective Response, Determined by an IRC on the Basis of PET and CT Scans [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days) ]
  5. Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of PET and CT Scans [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days) ]
  6. Percentage of Participants with Objective Response, Determined by an IRC on the Basis of CT Scans Alone [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days) ]
  7. Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of CT Scans Alone [ Time Frame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle:21days) ]
  8. Percentage of Participants with Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone [ Time Frame: Baseline up to 5 years ]
  9. Observed Serum Obinutuzumab Concentration [ Time Frame: Pre-infusion (0 hour [hr]) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description. ]
    Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose), 0.5 hr post-infusion on Day 1 on Cycles 2, 4, 6; Post-induction: pre-infusion (within 5 hr before dose) on Day 1 of Months 2, 8, 14, 20; at treatment discontinuation (up to Month 24), 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 1-2 days) (1 cycle: 21 days)

  10. Observed Serum Rituximab Concentration [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 0.5 hr post-infusion on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description. ]
    Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 of Cycles 2, 4; pre-infusion (-5 hr), 0.5 hr post-infusion on Day 1 of Cycle 6 (infusion duration: 60-90 minutes) (1 cycle: 21 days)

  11. Observed Serum Polatuzumab Vedotin Concentration [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description. ]
    Induction: pre-infusion (0 hr) on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 on Cycles 2, 4; Post-induction: at treatment discontinuation (up to Month 24); 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 90 minutes) (1 cycle: 21 days)

  12. Observed Plasma Polatuzumab Vedotin Concentration [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description. ]
    Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day 1 of Cycle 1; Cycle 1 Days 8, 15; pre-infusion (within 5 hr prior to dose), 0.5 hr post-infusion on Day 1 on Cycles 2, 4; pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6 (infusion duration: 90 minutes) (1 cycle: 21 days)

  13. Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description. ]
    Induction: pre-infusion (0 hr) on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 on Cycles 2, 4; Post-induction: at treatment discontinuation (up to Month 24); 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 90 minutes) (1 cycle: 21 days)

  14. Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE) [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description. ]
    Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day 1 of Cycle 1; Cycle 1 Days 8, 15; pre-infusion (within 5 hr prior to dose), 0.5 hr post-infusion on Day 1 on Cycles 2, 4; pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6 (infusion duration: 90 minutes) (1 cycle: 21 days)

  15. Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description. ]
    Induction: pre-infusion (0 hr), 0.5 hr post-infusion on Day 1 of Cycle 1; Cycle 1 Days 8, 15; pre-infusion (within 5 hr prior to dose), 0.5 hr post-infusion on Day 1 on Cycles 2, 4; pre-infusion (within 5 hr prior to dose) on Day 1 of Cycle 6 (infusion duration: 90 minutes) (1 cycle: 21 days)

  16. Observed Plasma Venetoclax Concentration [ Time Frame: 4 hr post-dose on Day 1 of Cycle 1 up to pre-dose (within 1 hr prior to dose) on Day 1 of Cycle 6. Detailed timeframe is given in outcome measure description. ]
    Induction: 4 hr post-dose on Day 1 of Cycle 1, pre-dose (within 1 hr prior to dose) and 2, 4, 6, and 8 hr post-dose on Day 1 of Cycle 2, pre-dose (within 1 hr prior to dose) on Day 1 of Cycles 4, and 6 (1 cycle: 21 days)

  17. Percentage of Participants with Human Anti-Human Antibodies (HAHAs) to Obinutuzumab [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description. ]
    Induction: pre-infusion (0 hr) on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 on Cycle 6; Post-induction: at treatment discontinuation (up to Month 24), 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 1-2 days) (1 cycle: 21 days)

  18. Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to maximum 5 years. Detailed timeframe is given in outcome measure description. ]
    Induction: pre-infusion (0 hr) on Day 1 of Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 on Cycles 2, 4; Post-induction: at treatment discontinuation (up to Month 24), 120 days and 1-2 years post-last dose (maximum up to 5 years) (infusion duration: 1-2 days) (1 cycle: 21 days)

  19. Recommended Phase 2 Dose (RP2D) of Polatuzumab Vedotin [ Time Frame: Baseline up to 21 days ]
  20. Recommended Phase 2 Dose (RP2D) of Venetoclax [ Time Frame: Baseline up to 21 days ]
  21. Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Baseline up to 21 days ]
  22. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • For obinutuzumab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) (anti-CD20) monoclonal antibody (mAb) and for which no other more appropriate treatment option exists, as determined by the investigator
  • For rituximab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 mAb and for which no curative option exists as determined by the investigator
  • At least one bidimensionally measurable lesion

Exclusion Criteria:

  • Known CD20-negative status at relapse or progression
  • Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
  • Grade 3b FL
  • History of transformation of indolent disease to DLBCL
  • Current use of systemic corticosteroids greater than (>) 20 milligrams (mg) prednisone per day (or equivalent); or prior anti-cancer therapy to include: radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
  • Central nervous system (CNS) disease
  • Active infection
  • Actual or potential cytochrome P450 (CYP) 3A interactions including: requirement for warfarin; use of strong and moderate CYP3A inhibitors or inducers within 7 days prior to first dose of venetoclax; or consumption of grapefruit, Seville oranges, or star fruit within 3 days prior to first dose of venetoclax
  • Positive for human immunodeficiency virus (HIV) or hepatitis B or C
  • Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1
  • Poor hematologic, renal, or hepatic function
  • Pregnant or lactating women
  • Life expectancy <3 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02611323


Contacts
Contact: Reference Study ID Number: GO29833 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 22 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02611323     History of Changes
Other Study ID Numbers: GO29833
2015-001998-40 ( EudraCT Number )
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: November 30, 2018
Last Verified: November 2018

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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Obinutuzumab
Venetoclax
Rituximab
Antibodies, Monoclonal
Immunoconjugates
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents