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Completed

NCT Number: NCT02631577

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

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.

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Key information

Conditions

Lymphoma, Follicular Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Chu Toulouse, Bron, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Atezolizumab (MPDL3280A) [TECENTRIQ]

Drug

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.

Lenalidomide

Drug

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.

Obinutuzumab

Drug

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 outcomes

  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 outcomes

  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 as Determined by the IRC and Investigator on the Basis of PET-CT Scans

    Time frame: 6 months (up to CCOD of 23 October 2018)

    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.

  4. 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

    Time frame: 6 months (up to CCOD of 23 October 2018)

    Objective response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the IRC and by the Investigator.

  5. Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone

    Time frame: 30 months

    Best Response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the Investigator.

  6. Percentage of Participants With Adverse Events and Serious Adverse Events

    Time frame: Baseline up to approximately 59 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.

  7. 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

  8. Serum Concentration of Obinutuzumab (mcg/mL)

    Time frame: Baseline up to approximately 59 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 Atezolizumab (mcg/mL)

    Time frame: Baseline up to approximately 59 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

  10. Serum Concentration of Lenalidomide (ng/mL)

    Time frame: Baseline up to approximately 59 months

    The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; HR = Hour

  11. Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab

    Time frame: Baseline up to approximately 59 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. All baseline and post-baseline samples from participants were negative for HAHAs to obinutuzumab and the results are shown below.

  12. Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab

    Time frame: Baseline up to approximately 59 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. All baseline and post-baseline samples were negative for ATAs to atezolizumab and the results are shown below.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2018
Study completion
2020
First posted
Dec 16, 2015
Registry last updated
Apr 13, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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