Clinical trial NCT02631577: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma, Follicular
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-12-16
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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
timeFrame: 6 months (up to clinical cut-off date (CCOD) of 23 October 2018)
Secondary outcomes:
measure: Percentage of Participants Achieving CR at EOI, as Determined by the Investigator Using Modified Lugano 2014 Criteria
timeFrame: 6 months (up to CCOD of 23 October 2018)
measure: Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria
timeFrame: 6 months (up to CCOD of 23 October 2018)
measure: 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
timeFrame: 6 months (up to CCOD of 23 October 2018)
measure: 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
timeFrame: 6 months (up to CCOD of 23 October 2018)
measure: Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone
timeFrame: 30 months
measure: Percentage of Participants With Adverse Events and Serious Adverse Events
timeFrame: Baseline up to approximately 59 months
measure: Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment
timeFrame: Day 1 - Day 28 of second cycle
measure: Serum Concentration of Obinutuzumab (mcg/mL)
timeFrame: Baseline up to approximately 59 months
measure: Serum Concentration of Atezolizumab (mcg/mL)
timeFrame: Baseline up to approximately 59 months
measure: Serum Concentration of Lenalidomide (ng/mL)
timeFrame: Baseline up to approximately 59 months
measure: Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab
timeFrame: Baseline up to approximately 59 months
measure: Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab
timeFrame: Baseline up to approximately 59 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Miami
country: United States
facility: University Miami
state: Florida
city: Louisville
country: United States
facility: Norton Medical Plaza II
state: Kentucky
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Bron
country: France
facility: Chu Toulouse
city: Creteil
country: France
facility: Hopital Henri Mondor; 51 Av Mal Lattre De Tassigny
city: Dijon
country: France
facility: Hopital du Bocage
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
city: Lille
country: France
facility: CHRU de Lille - Hopital Claude Huriez
city: Montpellier
country: France
facility: CHU Montpellier - Saint ELOI
city: Nantes
country: France
facility: CHU - Hôtel Dieu hematolgie clinique
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud; Hematolgie
city: Rennes
country: France
facility: CHU de Rennes - Hopital de Pontchaillo
city: Rouen
country: France
facility: Centre Henri Becquerel
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: