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A Study Evaluating the Safety and Efficacy of Atezolizumab in Combination With Obinutuzumab Plus Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02631577
Recruitment Status : Active, not recruiting
First Posted : December 16, 2015
Results First Posted : December 30, 2019
Last Update Posted : April 16, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will evaluate the safety, efficacy, pharmacokinetics and immunogenicity of induction treatment consisting of atezolizumab in combination with obinutuzumab plus lenalidomide in patients with relapsed or refractory follicular lymphoma (FL), followed by maintenance treatment with atezolizumab plus obinutzumab plus lenalidomide in patients who achieve a complete response (CR), a partial response (PR), or stable disease at end of induction.

Condition or disease Intervention/treatment Phase
Lymphoma, Follicular Drug: Atezolizumab (MPDL3280A) [TECENTRIQ] Drug: Lenalidomide Drug: Obinutuzumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 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 Atezolizumab in Combination With Obinutuzumab Plus Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma
Actual Study Start Date : December 31, 2015
Actual Primary Completion Date : October 23, 2018
Estimated Study Completion Date : September 18, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Atezolizumab-G-lena 15mg
Participants were administered obinutuzumab, Atezolizumab, and 15 mg of Lenalidomide.
Drug: Atezolizumab (MPDL3280A) [TECENTRIQ]
Atezolizumab will be administered at a flat dose of 840 mg on Days 1 and 15 of Cycles 2 to 6, given in 28-day cycles as induction treatment and 840 mg on Days 1 and 2 of each month, given as maintenance treatment.

Drug: Lenalidomide
Lenalidomide will be administered orally once daily on Days 1 to 21 of Cycles 1 to 6 (28-day cycles) during induction treatment and on Days 1 to 21 of each month during maintenance treatment. Lenalidomide will be administered at a dose of 15 or 20 mg (dose may be de-escalated to 10 mg) during induction treatment and at 10 mg during maintenance treatment. During the expansion phase, lenalidomide will be administered at the RP2D during induction treatment and at 10 mg during maintenance treatment.

Drug: Obinutuzumab
Obinutuzumab will be administered by intravenous infusion at an absolute (flat) dose of 1000 mg on Days 1, 8, and 15 of the first cycle and on Day 1 of each subsequent cycle during induction treatment, and on Day 1 of every other month (i.e., every 2 months) during maintenance treatment.

Experimental: Atezolizumab-G-lena 20mg
Participants were administered obinutuzumab, Atezolizumab, and 20 mg of Lenalidomide.
Drug: Atezolizumab (MPDL3280A) [TECENTRIQ]
Atezolizumab will be administered at a flat dose of 840 mg on Days 1 and 15 of Cycles 2 to 6, given in 28-day cycles as induction treatment and 840 mg on Days 1 and 2 of each month, given as maintenance treatment.

Drug: Lenalidomide
Lenalidomide will be administered orally once daily on Days 1 to 21 of Cycles 1 to 6 (28-day cycles) during induction treatment and on Days 1 to 21 of each month during maintenance treatment. Lenalidomide will be administered at a dose of 15 or 20 mg (dose may be de-escalated to 10 mg) during induction treatment and at 10 mg during maintenance treatment. During the expansion phase, lenalidomide will be administered at the RP2D during induction treatment and at 10 mg during maintenance treatment.

Drug: Obinutuzumab
Obinutuzumab will be administered by intravenous infusion at an absolute (flat) dose of 1000 mg on Days 1, 8, and 15 of the first cycle and on Day 1 of each subsequent cycle during induction treatment, and on Day 1 of every other month (i.e., every 2 months) during maintenance treatment.




Primary Outcome Measures :
  1. Percentage of Participants Achieving Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria [ Time Frame: 6 months (up to clinical cut-off date (CCOD) of 23 October 2018) ]
    Complete response (CR) was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the IRC.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving CR at EOI, as Determined by the Investigator Using Modified Lugano 2014 Criteria [ Time Frame: 6 months (up to CCOD of 23 October 2018) ]
    CR was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the Investigator.

  2. Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria [ Time Frame: 6 months (up to CCOD of 23 October 2018) ]
    CR was evaluated through use of CT scans, using the Lugano 2014 criteria. Response was determined by the IRC and by the Investigator.

  3. Percentage of Participants With Objective Response (CR or PR) at EOI [ Time Frame: 6 months (up to CCOD of 23 October 2018) ]
    Objective response was evaluated through use of PET-CT scans or CT scans alone, using the Lugano 2014 or modified Lugano 2014 criteria. Response was determined by the IRC and by the Investigator.

  4. Percentage of Participants With Objective Response (CR or PR) During the Study [ Time Frame: 30 months ]
  5. Percentage of Participants With Adverse Events and Serious Adverse Events [ Time Frame: 30 months ]
    An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

  6. Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment [ Time Frame: Day 1 - Day 28 of second cycle ]
    Does limiting toxicity (DLT) is defined as any one of the following events occurring during Cycle 2 of treatment and assessed by the investigator as related to study treatment: - Adverse event of any grade that leads to a delay of more than 14 days at the start of the next treatment cycle; - Hematologic adverse events (neutropenia, thrombocytopenia); - Non-hematologic adverse event, except IRRs, diarrhea, nausea or vomiting

  7. Serum Concentration of Obinutuzumab (mcg/mL) [ Time Frame: From Baseline up to 30 months ]
    The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year

  8. Serum Concentration of Atezolizumab (mcg/mL) [ Time Frame: From Baseline up to 30 months ]
    The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year

  9. Serum Concentration of Lenalidomide (ng/mL) [ Time Frame: From Baseline up to 30 months ]
    The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; HR = Hour

  10. Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab [ Time Frame: From Baseline up to 30 months ]
    The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year

  11. Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab [ Time Frame: From Baseline up to 30 months ]
    The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year



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.


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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:

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
  • Relapsed or refractory 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
  • Histologically documented CD20-positive lymphoma as determined by the local laboratory
  • Fluorodeoxyglucose-avid lymphoma (i.e., PET-positive lymphoma)
  • At least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan or magnetic resonance imaging [MRI])
  • Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL
  • Agreement to comply with all local requirements of the lenalidomide risk minimization plan
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), and for at least 18 months after the last dose of study treatment
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm for at least 3 months after the last dose of study treatment

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 lymphoma or leptomeningeal infiltration
  • Prior allogeneic stem-cell transplantation (SCT)
  • Completion of autologous SCT within 100 days prior to Day (D) 1 of Cycle (C) 1
  • Prior standard or investigational anti-cancer therapy as specified in protocol
  • History of resistance to lenalidomide or response duration of <1 year
  • Treatment with systemic immunosuppressive medications
  • History of solid organ transplantation
  • Clinically significant toxicity from prior therapy that has not resolved to Grade <=2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE], v4.0) prior to Day 1 of Cycle 1
  • History of erythema multiforme, Grade >= 3 rash, or blistering following prior treatment with immunomodulatory derivatives such as thalidomide and lenalidomide
  • Active bacterial, viral, fungal, or other infection
  • Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening
  • Known history of HIV positive status
  • History of progressive multifocal leukoencephalopathy
  • History of autoimmune disease
  • Contraindication to treatment for TE prophylaxis
  • Grade <= 2 neuropathy
  • History of other malignancy that could affect compliance with the protocol or interpretation of results
  • Evidence of any significant, uncontrolled concomitant disease
  • Inadequate hematologic function (unless due to underlying lymphoma)
  • Abnormal laboratory values (unless due to underlying lymphoma)
  • Pregnant or lactating or intending to become pregnant during the study

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): NCT02631577


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-0017
United States, Florida
University Miami
Miami, Florida, United States, 33136
United States, Kentucky
Norton Medical Plaza II
Louisville, Kentucky, United States, 40207
United States, New York
Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
New York, New York, United States, 10065
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
France
Hopital Henri Mondor; 51 Av Mal Lattre De Tassigny
Creteil, France, 94010
Hopital du Bocage
Dijon, France, 21034
Centre Jean Bernard
Le Mans, France, 72015
Centre Hospitalier Le Mans
Le Mans, France, 72037
CHRU de Lille - Hopital Claude Huriez
Lille, France, 59037
CHU Montpellier - Saint ELOI
Montpellier, France, 34295
CHU - Hôtel Dieu hematolgie clinique
Nantes, France, 44093
Centre Hospitalier Lyon Sud; Hematolgie
Pierre Benite, France, 69495
CHU de Rennes - Hopital de Pontchaillo
Rennes, France, 35033
Centre Henri Becquerel
Rouen, France, 76038
Chu Toulouse
Toulouse, France, 31059
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02631577    
Other Study ID Numbers: BO29562
2015-002467-42 ( EudraCT Number )
First Posted: December 16, 2015    Key Record Dates
Results First Posted: December 30, 2019
Last Update Posted: April 16, 2020
Last Verified: April 2020
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lenalidomide
Atezolizumab
Obinutuzumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Immunological