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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

Primary Purpose

Lymphoma, Follicular

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Atezolizumab (MPDL3280A) [TECENTRIQ]
Lenalidomide
Obinutuzumab
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Follicular

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • University Miami
  • Norton Medical Plaza II
  • Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
  • Levine Cancer Institute
  • Chu Toulouse
  • Hopital Henri Mondor; 51 Av Mal Lattre De Tassigny
  • Hopital du Bocage
  • Centre Jean Bernard
  • Centre Hospitalier Le Mans
  • CHRU de Lille - Hopital Claude Huriez
  • CHU Montpellier - Saint ELOI
  • CHU - Hôtel Dieu hematolgie clinique
  • Centre Hospitalier Lyon Sud; Hematolgie
  • CHU de Rennes - Hopital de Pontchaillo
  • Centre Henri Becquerel

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Atezolizumab-G-lena 15mg

Atezolizumab-G-lena 20mg

Arm Description

Participants were administered obinutuzumab, Atezolizumab, and 15 mg of Lenalidomide.

Participants were administered obinutuzumab, Atezolizumab, and 20 mg of Lenalidomide.

Outcomes

Primary Outcome Measures

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
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

Percentage of Participants Achieving CR at EOI, as Determined by the Investigator Using Modified Lugano 2014 Criteria
CR was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the Investigator.
Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria
CR was evaluated through use of CT scans, using the Lugano 2014 criteria. Response was determined by the IRC and by the Investigator.
Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans
Objective response was evaluated through use of PET-CT scans, using the Lugano 2014 or modified Lugano 2014 criteria. Response was determined by the IRC and by the Investigator.
Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of CT Scans Alone
Objective response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the IRC and by the Investigator.
Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone
Best Response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the Investigator.
Percentage of Participants With Adverse Events and Serious Adverse Events
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.
Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment
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
Serum Concentration of Obinutuzumab (mcg/mL)
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
Serum Concentration of Atezolizumab (mcg/mL)
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
Serum Concentration of Lenalidomide (ng/mL)
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; HR = Hour
Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab
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. All baseline and post-baseline samples from participants were negative for HAHAs to obinutuzumab and the results are shown below.
Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab
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. All baseline and post-baseline samples were negative for ATAs to atezolizumab and the results are shown below.

Full Information

First Posted
December 14, 2015
Last Updated
April 11, 2022
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02631577
Brief Title
A Study Evaluating the Safety and Efficacy of Atezolizumab in Combination With Obinutuzumab Plus Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
December 31, 2015 (Actual)
Primary Completion Date
October 23, 2018 (Actual)
Study Completion Date
October 7, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Follicular

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atezolizumab-G-lena 15mg
Arm Type
Experimental
Arm Description
Participants were administered obinutuzumab, Atezolizumab, and 15 mg of Lenalidomide.
Arm Title
Atezolizumab-G-lena 20mg
Arm Type
Experimental
Arm Description
Participants were administered obinutuzumab, Atezolizumab, and 20 mg of Lenalidomide.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab (MPDL3280A) [TECENTRIQ]
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
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 Measure Information:
Title
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
Description
Complete response (CR) was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the IRC.
Time Frame
6 months (up to clinical cut-off date (CCOD) of 23 October 2018)
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving CR at EOI, as Determined by the Investigator Using Modified Lugano 2014 Criteria
Description
CR was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the Investigator.
Time Frame
6 months (up to CCOD of 23 October 2018)
Title
Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria
Description
CR was evaluated through use of CT scans, using the Lugano 2014 criteria. Response was determined by the IRC and by the Investigator.
Time Frame
6 months (up to CCOD of 23 October 2018)
Title
Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans
Description
Objective response was evaluated through use of PET-CT scans, using the Lugano 2014 or modified Lugano 2014 criteria. Response was determined by the IRC and by the Investigator.
Time Frame
6 months (up to CCOD of 23 October 2018)
Title
Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of CT Scans Alone
Description
Objective response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the IRC and by the Investigator.
Time Frame
6 months (up to CCOD of 23 October 2018)
Title
Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone
Description
Best Response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the Investigator.
Time Frame
30 months
Title
Percentage of Participants With Adverse Events and Serious Adverse Events
Description
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.
Time Frame
Baseline up to approximately 59 months
Title
Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment
Description
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
Time Frame
Day 1 - Day 28 of second cycle
Title
Serum Concentration of Obinutuzumab (mcg/mL)
Description
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
Time Frame
Baseline up to approximately 59 months
Title
Serum Concentration of Atezolizumab (mcg/mL)
Description
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
Time Frame
Baseline up to approximately 59 months
Title
Serum Concentration of Lenalidomide (ng/mL)
Description
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; HR = Hour
Time Frame
Baseline up to approximately 59 months
Title
Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab
Description
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. All baseline and post-baseline samples from participants were negative for HAHAs to obinutuzumab and the results are shown below.
Time Frame
Baseline up to approximately 59 months
Title
Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab
Description
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. All baseline and post-baseline samples were negative for ATAs to atezolizumab and the results are shown below.
Time Frame
Baseline up to approximately 59 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Norton Medical Plaza II
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Chu Toulouse
City
Bron
ZIP/Postal Code
69500
Country
France
Facility Name
Hopital Henri Mondor; 51 Av Mal Lattre De Tassigny
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Hopital du Bocage
City
Dijon
ZIP/Postal Code
21034
Country
France
Facility Name
Centre Jean Bernard
City
Le Mans
ZIP/Postal Code
72015
Country
France
Facility Name
Centre Hospitalier Le Mans
City
Le Mans
ZIP/Postal Code
72037
Country
France
Facility Name
CHRU de Lille - Hopital Claude Huriez
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
CHU Montpellier - Saint ELOI
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
CHU - Hôtel Dieu hematolgie clinique
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Centre Hospitalier Lyon Sud; Hematolgie
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
CHU de Rennes - Hopital de Pontchaillo
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France

12. IPD Sharing Statement

Learn more about this trial

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

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