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

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ClinicalTrials.gov Identifier: NCT02600897
Recruitment Status : Recruiting
First Posted : November 9, 2015
Last Update Posted : July 18, 2019
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 lenalidomide in participants with relapsed or refractory (R/R) follicular lymphoma (FL) and rituximab in combination with polatuzumab vedotin and lenalidomide in participants with R/R diffuse large B-cell lymphoma (DLBCL), followed by post-induction treatment with obinutuzumab in combination with lenalidomide in participants with FL who achieve a complete response (CR), partial response (PR), or stable disease (SD) at end of induction (EOI) and post-induction treatment with rituximab plus lenalidomide in participants with DLBCL who achieve a CR or PR at EOI.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma Drug: Lenalidomide Drug: Obinutuzumab Drug: Polatuzumab Vedotin Drug: Rituximab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 128 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 Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Actual Study Start Date : March 23, 2016
Estimated Primary Completion Date : August 29, 2019
Estimated Study Completion Date : February 23, 2022


Arm Intervention/treatment
Experimental: Dose-escalation Cohort: FL
Participants with R/R FL will receive 6 months of induction treatment with polatuzumab vedotin and lenalidomide at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and lenalidomide when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 24-month maintenance regimen consisting of lenalidomide and obinutuzumab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).
Drug: Lenalidomide
All participants will receive lenalidomide oral capsules at doses of 10, 15, or 20 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by post-induction treatment at a dose of 10 mg once daily on Days 1 to 21 of each subsequent 28-day cycle. Post-induction lenalidomide may continue for up to 12 months until disease progression or unacceptable toxicity for participants with R/R FL and up to 6 months until disease progression or unacceptable toxicity for participants with R/R DLBCL.

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 followed by post-induction treatment 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.

Drug: Polatuzumab Vedotin
Participants with R/R FL will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) on Day 1 of each 28-day cycle for up to 6 months during induction treatment. Participants wit R/R DLBCL will receive polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 months during induction treatment.

Experimental: Dose-escalation Cohort: DLBCL
Participants with R/R DLBCL will receive 6 months of induction treatment with fixed dose of polatuzumab vedotin and rituximab along with dose escalating lenalidomide. Lenalidomide will be administered at escalating doses to identify the recommended Phase 2 dose (RP2D) for lenalidomide. Those who achieve CR and PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 6-month consolidation regimen consisting of lenalidomide and rituximab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).
Drug: Lenalidomide
All participants will receive lenalidomide oral capsules at doses of 10, 15, or 20 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by post-induction treatment at a dose of 10 mg once daily on Days 1 to 21 of each subsequent 28-day cycle. Post-induction lenalidomide may continue for up to 12 months until disease progression or unacceptable toxicity for participants with R/R FL and up to 6 months until disease progression or unacceptable toxicity for participants with R/R DLBCL.

Drug: Polatuzumab Vedotin
Participants with R/R FL will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) on Day 1 of each 28-day cycle for up to 6 months during induction treatment. Participants wit R/R DLBCL will receive polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 months during induction treatment.

Drug: Rituximab
Participants will receive a fixed dose of rituximab, 375 mg/m^2 via intravenous (IV) infusion to be given on Days 1 of Cycle 1 to 6 followed by post-induction treatment at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month for up to 6 months, until disease progression or unacceptable toxicity.

Experimental: Expansion Cohort: FL
Participants with R/R FL who received induction treatment with polatuzumab vedotin and lenalidomide, in addition to obinutuzumab and achieved CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 24-months maintenance regimen consisting of lenalidomide and obinutuzumab for first 12 months followed by obinutuzumab treatment for next 12 months. Post-induction therapy will start 8 weeks after Cycle 6 Day 1.
Drug: Lenalidomide
All participants will receive lenalidomide oral capsules at doses of 10, 15, or 20 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by post-induction treatment at a dose of 10 mg once daily on Days 1 to 21 of each subsequent 28-day cycle. Post-induction lenalidomide may continue for up to 12 months until disease progression or unacceptable toxicity for participants with R/R FL and up to 6 months until disease progression or unacceptable toxicity for participants with R/R DLBCL.

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 followed by post-induction treatment 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 R/R DLBCL who received induction treatment with polatuzumab vedotin and lenalidomide in addition to rituximab and achieved CR or PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 6-month consolidation regimen consisting of lenalidomide and rituximab. Post-induction therapy will start 8 weeks after Cycle 6 Day 1.
Drug: Lenalidomide
All participants will receive lenalidomide oral capsules at doses of 10, 15, or 20 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by post-induction treatment at a dose of 10 mg once daily on Days 1 to 21 of each subsequent 28-day cycle. Post-induction lenalidomide may continue for up to 12 months until disease progression or unacceptable toxicity for participants with R/R FL and up to 6 months until disease progression or unacceptable toxicity for participants with R/R DLBCL.

Drug: Rituximab
Participants will receive a fixed dose of rituximab, 375 mg/m^2 via intravenous (IV) infusion to be given on Days 1 of Cycle 1 to 6 followed by post-induction treatment at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month for up to 6 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 28 weeks) ]

Secondary Outcome Measures :
  1. Percentage of Participants with Adverse Events [ Time Frame: Up to approximately 3 years ]
  2. Percentage of participants with dose-limiting toxicities (DLTs) [ Time Frame: Up to approximately 3 years ]
  3. 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) ]
  4. Percentage of Participants with CR, Determined by the Independent Review Committee (IRC) and 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) ]
  5. Percentage of Participants with Objective Response, Determined by the IRC and 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) ]
  6. Percentage of Participants with Objective Response, Determined by the IRC and 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) ]
  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 28 weeks) ]
  8. Percentage of Participants With Best Response of Clinical Response (CR) or Partial Response (PR), Determined by the Investigator on the Basis of CT Scans Alone [ Time Frame: Up to approximately 3 years ]
  9. Observed Serum Obinutuzumab Concentration [ Time Frame: Pre-dose and/or 30 minutes post-dose on Day 1 of Cycles 1, 2, 4, and 6 during induction; pre-dose on Day 1 of Months 1, 7, 13, and/or 19 during the post-induction phase; then up to 2 years after last dose as available (maximum 5 years) ]
  10. Observed Serum Rituximab Concentration [ Time Frame: Pre-dose and/or 30 minutes post-dose on Day 1 of Cycles 1, 2, 4, and 6 during induction; pre-dose on Day 1 of Months 1, 7, 13, and/or 19 during the post-induction phase; then up to 2 years after last dose as available (maximum 5 years) ]
  11. Observed Serum and Plasma Polatuzumab Vedotin Concentration [ Time Frame: Pre-dose and/or 30 minutes post-dose on Days 1, 8, and 15 of Cycle 1; pre-dose and/or 30 minutes post-dose on Day 1 of Cycles 2, 4, and 6 during induction; then up to 2 years after last dose as available (maximum 5 years) ]
  12. Observed Plasma Lenalidomide Concentration [ Time Frame: Pre-dose and/or 0.5, 1, 2, 4, and 8 hours post-dose on Days 1 and 15 of Cycle 1 and on Day 1 of Cycle 6 (maximum 5 years) ]
  13. Percentage of Participants with Human Anti-human Antibodies (HAHAs) to Obinutuzumab [ Time Frame: Pre-dose on Day 1 of Cycles 1 and 6 during induction; then up to 2 years after last dose as available (maximum 5 years) ]
  14. Percentage of Participants with Human Anti-chimeric Antibodies (HACAs) to Rituximab [ Time Frame: Pre-dose on Day 1 of Cycles 1 and 6 during induction; then up to 2 years after last dose as available (maximum 5 years) ]
  15. Percentage of Participants with Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin [ Time Frame: Pre-dose on Day 1 of Cycles 1, 2, and 4 during induction; then up to 2 years after last dose as available (maximum 5 years) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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
  • For obinutuzumab in combination with polatuzumab vedotin and lenalidomide (G + Pola + Len) treatment group: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
  • For rituximab in combination with polatuzumab vedotin and lenalidomide (R + Pola + Len) treatment group: R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in patients who are not eligible for autologous stem-cell transplantation or who have experienced disease progression following treatment with high-dose chemotherapy plus autologous stem-cell transplantation
  • Histologically documented CD20-positive B-cell lymphoma as determined by the local laboratory
  • fluorodeoxyglucose (FDG)-avid lymphoma (i.e., positron emission tomography (PET)-positive lymphoma)
  • At least one bi-dimensionally measurable lesion
  • Agreement to remain abstinent or use adequate contraception, among women or men of childbearing potential

Exclusion Criteria:

  • Grade 3b follicular lymphoma
  • History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
  • Known CD20-negative status at relapse or progression
  • Central nervous system (CNS) lymphoma or leptomeningeal infiltration
  • Prior allogeneic stem-cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
  • Current use of systemic immunosuppressant(s), or prior anti-cancer therapy to include: lenalidomide, fludarabine, or alemtuzumab within 12 months; 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
  • 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
  • Life expectancy less than (<) 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): NCT02600897


Contacts
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Contact: Reference Study ID Number: GO29834 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
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United States, Georgia
Northwest Georgia Oncology Centers Completed
Marietta, Georgia, United States, 30060
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
United States, Missouri
University of Missouri/Ellis Fischel Completed
Columbia, Missouri, United States, 65212
Washington University; Wash Uni. Sch. Of Med Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
NYU School of Medicine Recruiting
New York, New York, United States, 10016
United States, Texas
Rocky Mountain Cancer Centers, LLP Recruiting
Irving, Texas, United States, 75063
Texas Oncology-Tyler Recruiting
Irving, Texas, United States, 75063
Texas Oncology San Antonio Medical Center Recruiting
San Antonio, Texas, United States, 78229
Spain
Insititut Catala D'Oncologia Recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08908
Hospital Clínico Málaga Recruiting
Málaga, Malaga, Spain, 29010
Complejo Hospitalario de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Clínica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31620
Hospital Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Hospital Clínic. Barcelona Recruiting
Barcelona, Spain, 08036
Hospital Gregorio Marañon Recruiting
Madrid, Spain, 28007
Hospital Universitario Fundacion Jimenez Diaz. Recruiting
Madrid, Spain, 28040
Hospital Universitario Virgen del Rocio; Servicio de Hematologia Withdrawn
Sevilla, Spain, 41013
Hospital La Fe Recruiting
Valencia, Spain
United Kingdom
St James University Hospital Recruiting
Leeds, United Kingdom, LS9 7TF
University Hospitals of Leicester NHS Trust - Leicester Royal Infirmary Recruiting
Leicester, United Kingdom, LE1 5WW
Royal Liverpool University Hospital Recruiting
Liverpool, United Kingdom, L7 8XP
Barts Hospital; Institute of Cancer Recruiting
London, United Kingdom, EC1M 6BQ
Sarah Cannon Research Institute Recruiting
London, United Kingdom, W1G 6AD
Maidstone & Tonbridge Wells Hospital; Kent Oncology Center Recruiting
Maidstone, United Kingdom, ME16 9QQ
Nottingham University Hospitals NHS Trust - City Hospital Recruiting
Nottingham, United Kingdom, NG5 1PB
Barking, Havering and Redbridge University Hospitals NHS Trust - Queen's Hospital Completed
Romford, United Kingdom, RM7 0AG
The Royal Wolverhampton Hospitals NHS Trust; Department of Haematology Recruiting
Wolverhampton, United Kingdom, WV10 0QP
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02600897     History of Changes
Other Study ID Numbers: GO29834
2015-001999-22 ( EudraCT Number )
First Posted: November 9, 2015    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019

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

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