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A Study of Obinutuzumab With Idasanutlin in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02624986
First received: December 1, 2015
Last updated: March 10, 2017
Last verified: March 2017
  Purpose
This study will evaluate the safety, efficacy, and pharmacokinetics of idasanutlin in combination with obinutuzumab in participants with relapsed or refractory FL or DLBCL. Participants with FL who achieve complete response (CR), partial response (PR), or stable disease (SD) at the end of induction therapy (EOI) will be eligible for post-induction treatment with obinutuzumab.

Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: Idasanutlin
Drug: Obinutuzumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Idasanutlin in Patients With Relapsed or Refractory Follicular Lymphoma or Diffuse Large B-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 28 weeks from Day 1 of Cycle 1) ]

Secondary Outcome Measures:
  • Percentage of participants with dose-limiting toxicities (DLTs) [ Time Frame: Up to approximately 2.5 years ]
  • 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 28 weeks from Day 1 of Cycle 1) ]
  • 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 28 weeks from Day 1 of Cycle 1) ]
  • 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 28 weeks from Day 1 of Cycle 1) ]
  • 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 28 weeks from Day 1 of Cycle 1) ]
  • 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 28 weeks from Day 1 of Cycle 1) ]
  • 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 28 weeks from Day 1 of Cycle 1) ]
  • Observed serum obinutuzumab concentration in participants with DLBCL [ Time Frame: Pre-dose/30 minutes post-dose on Day 1 of induction Cycles 1, 2, 4, and 6; discontinuation (up to 6 months); 120 days after last dose; and 1 to 2 years after last dose (maximum 2.5 years) ]
  • Observed serum obinutuzumab concentration in participants with FL [ Time Frame: Pre-dose/30 minutes post-dose on Day 1 of induction Cycles 1, 2, 4, and 6; pre-dose on Day 1 of Months 2, 8, 14, and/or 20 post-induction; discontinuation (up to 30 months); 120 days after last dose; and 1 to 2 years after last dose (maximum 4.5 years) ]
  • Observed plasma idasanutlin concentration [ Time Frame: Pre-dose and 6 hours post-dose on Day 1 of Cycles 1, 2, and 4 and on Day 5 of Cycles 2 and 4; pre-dose and 2, 4, and 6 hours post-dose on Day 5 of Cycle 1 ]
  • Percentage of participants with adverse events (AEs) [ Time Frame: Up to approximately 2.5 years ]

Estimated Enrollment: 120
Actual Study Start Date: December 23, 2015
Estimated Study Completion Date: May 15, 2022
Estimated Primary Completion Date: May 15, 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose-Escalation Cohort
Participants with DLBCL or FL will receive 6 cycles (28 days per cycle) of induction treatment with idasanutlin at escalating doses to identify the recommended Phase 2 dose (RP2D) when combined with a fixed dose of obinutuzumab. Those with FL who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen with obinutuzumab.
Drug: Idasanutlin
Participants will receive idasanutlin film-coated tablets at a starting dose of 100 milligrams (mg) daily on Days 1 to 5 of each 28-day cycle. Escalation will occur in at least 50-mg increments, and daily dosages >/=400 mg will be split into twice-daily dosing.
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 28 days. For eligible participants with FL, post-induction treatment may be given at a dose of 1000 mg via IV infusion on Day 1 of every other month for up to 24 months, until disease progression or unacceptable toxicity.
Experimental: Expansion Cohort: DLBCL
Participants with DLBCL will receive 6 cycles (28 days per cycle) of induction treatment with idasanutlin at the RP2D identified during the dose-escalation phase, in addition to obinutuzumab.
Drug: Idasanutlin
Participants will receive idasanutlin film-coated tablets at a starting dose of 100 milligrams (mg) daily on Days 1 to 5 of each 28-day cycle. Escalation will occur in at least 50-mg increments, and daily dosages >/=400 mg will be split into twice-daily dosing.
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 28 days. For eligible participants with FL, post-induction treatment may be given at a dose of 1000 mg via IV infusion on Day 1 of every other month for up to 24 months, until disease progression or unacceptable toxicity.
Experimental: Expansion Cohort: FL
Participants with FL will receive 6 cycles (28 days per cycle) of induction treatment with idasanutlin 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 with obinutuzumab.
Drug: Idasanutlin
Participants will receive idasanutlin film-coated tablets at a starting dose of 100 milligrams (mg) daily on Days 1 to 5 of each 28-day cycle. Escalation will occur in at least 50-mg increments, and daily dosages >/=400 mg will be split into twice-daily dosing.
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 28 days. For eligible participants with FL, post-induction treatment may be given at a dose of 1000 mg via IV infusion on Day 1 of every other month for up to 24 months, until disease progression or unacceptable toxicity.

  Eligibility

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

Inclusion Criteria:

  • Age greater than or equal to (>/=) 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Histologically documented cluster of differentiation (CD)20-positive B-cell lymphoma classified as relapsed or refractory FL or DLBCL after treatment with at least two prior chemoimmunotherapy regimens that included an anti-CD20 monoclonal antibody (mAb) and for which no other more appropriate treatment option exists
  • At least one bidimensionally measurable lesion
  • Agreement to remain abstinent or use adequate contraception, among women or men of childbearing potential

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
  • 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
  • Requirement for chronic anticoagulation
  • Central nervous system (CNS) disease
  • Active infection
  • 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
  • History of progressive multifocal leukoencephalopathy (PML)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02624986

Contacts
Contact: Reference Study ID Number: BH29812 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@roche.com

  Show 25 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Sai Li, M.D., Ph.D. Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02624986     History of Changes
Other Study ID Numbers: BH29812
2015-002100-83 ( EudraCT Number )
Study First Received: December 1, 2015
Last Updated: March 10, 2017

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
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 26, 2017