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A Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide in Patients With Follicular Lymphoma After at Least One Line of Systemic Therapy

NCT04712097

Description:

This study will evaluate the efficacy and safety of mosunetuzumab in combination with lenalidomide (M + Len) compared to rituximab in combination with lenalidomide (R + Len) in participants with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one line of prior systemic therapy.

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide in Patients With Follicular Lymphoma After at Least One Line of Systemic Therapy
  • Official Title: Phase III Randomized, Open-Label, Multicenter Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide in Patients With Follicular Lymphoma After at Least One Line of Systemic Therapy

Clinical Trial IDs

  • ORG STUDY ID: GO42909
  • SECONDARY ID: 2020-005239-53
  • NCT ID: NCT04712097

Conditions

  • Relapsed or Refractory Follicular Lymphoma

Interventions

DrugSynonymsArms
MosunetuzumabM + Len
LenalidomideM + Len
RituximabR + Len
TociluzumabM + Len

Purpose

This study will evaluate the efficacy and safety of mosunetuzumab in combination with lenalidomide (M + Len) compared to rituximab in combination with lenalidomide (R + Len) in participants with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one line of prior systemic therapy.

Trial Arms

NameTypeDescriptionInterventions
M + LenExperimentalParticipants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)
  • Mosunetuzumab
  • Lenalidomide
  • Tociluzumab
R + LenExperimentalParticipants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 6, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12)
  • Lenalidomide
  • Rituximab
  • Tociluzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

          -  Histologically documented CD20+ FL (Grades 1-3a)

          -  Meet Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria to receive systemic
             therapy

          -  Received at least 1 prior systemic lymphoma therapy (local radiotherapy is not
             considered systemic therapy)

          -  Availability of a representative tumor specimen and the corresponding pathology report
             at the time of relapse/persistence for confirmation of the diagnosis of FL.
             Pretreatment sample of at least 1 core-needle, excisional or incisional tumor biopsy
             is required. Cytological or fine-needle aspiration samples are not acceptable. Fresh
             pretreatment biopsy is preferred. Patients who are unable to undergo biopsy procedures
             may be eligible for study enrollment if an archival tumor tissue sample (preferably
             from the most recent relapse/persistence) as paraffin blocks or at least 15 unstained
             slides, or in accordance with local regulatory requirements, can be sent to the
             Sponsor.

          -  Adequate hematologic function (unless due to underlying lymphoma, per the
             investigator)

          -  For women of childbearing potential: Agreement to remain abstinent (refrain from
             heterosexual intercourse) or use 2 adequate methods of contraception, including at
             least 1 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 28 days after the last dose of lenalidomide, 3 months
             after the final dose of tocilizumab (if applicable), mosunetuzumab, and 12 months
             after final dose of rituximab. Women must refrain from donating eggs during this same
             period.

          -  For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures and agreement to refrain from donating sperm, as defined: With
             female partners of childbearing potential or pregnant female partners, men must remain
             abstinent or use a condom during the treatment period and for at least 28 days after
             last dose of lenalidomide, 3 months after the final dose of tocilizumab (if
             applicable), mosunetuzumab and 12 months after the final dose of rituximab. Men must
             refrain from donating sperm during this same period.

        Exclusion Criteria:

          -  Grade 3b FL

          -  History of transformation of indolent disease to diffuse-large B cell lymphoma

          -  Documented refractoriness to lenalidomide, defined as no response (partial response or
             complete response) or relapse within 6 months of therapy

          -  Active or history of CNS lymphoma or leptomeningeal infiltration

          -  Prior standard or investigational anti-cancer therapy as specified: Lenalidomide
             exposure within 12 months prior to Day 1 of Cycle 1; Chimeric antigen receptor T cell
             therapy within 30 days prior to Day 1 of Cycle 1; Radioimmunoconjugate within 12 weeks
             prior to Day 1 of Cycle 1; Monoclonal antibody or antibody-drug conjugate within 4
             weeks prior to Cycle 1 Day 1; Treatment with any anti-cancer agent (investigational or
             otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to
             first dose of study treatment

          -  Clinically significant toxicity (other than alopecia) from prior treatment that has
             not resolved to Grade </= 1 (per National Cancer Institute Common Terminology Criteria
             for Adverse Events, Version 5.0) prior to Day 1 of Cycle 1

          -  Treatment with systemic immunosuppressive medications, including, but not limited to
             prednisone (> 20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
             factor agents within 2 weeks prior to Day 1 of Cycle 1

          -  History of solid organ transplantation

          -  History of severe allergic or anaphylactic reaction to humanized, chimeric or murine
             monoclonal antibodies

          -  Known sensitivity or allergy to murine products

          -  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
             or any component of the mosunetuzumab, lenalidomide, or thalidomide formulation,
             including mannitol

          -  History of erythema multiforme, Grade >/= 3 rash, or blistering following prior
             treatment with immunomodulatory derivatives

          -  Known active bacterial, viral, fungal, or other infection, or any major episode of
             infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1

          -  Known or suspected chronic active Epstein-Barr virus (EBV) infection

          -  Known or suspected history of hemophagocytic lymphohistiocytosis

          -  Clinically significant history of liver disease, including viral or other hepatitis,
             or cirrhosis

          -  Active Hepatitis B infection

          -  Active Hepatitis C infection

          -  Known history of HIV positive status

          -  History of progressive multifocal leukoencephalopathy (PML)

          -  Administration of a live, attenuated vaccine within 4 weeks before first dose of study
             treatment or anticipation that such a live attenuated vaccine will be required during
             the study

          -  Other malignancy that could affect compliance with the protocol or interpretation of
             results

          -  Active autoimmune disease requiring treatment

          -  History of autoimmune disease, including, but not limited to: myocarditis,
             pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
             syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or
             glomerulonephritis

          -  Prior allogeneic stem cell transplantation

          -  Contraindication to treatment for thromboembolism prophylaxis

          -  Evidence of any significant, uncontrolled concomitant disease that could affect
             compliance with the protocol or interpretation of results, including, but not limited
             to, significant cardiovascular disease (e.g., New York Heart Association Class III or
             IV cardiac disease, myocardial infarction within the previous 6 months, unstable
             arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive
             pulmonary disease or history of bronchospasm)

          -  Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of
             Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the
             study

          -  Pregnant or lactating or intending to become pregnant during the study

          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the
             investigator's judgment, precludes the patient's safe participation in and completion
             of the study, or which could affect compliance with the protocol or interpretation of
             results
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) according to 2014 Lugano Response Criteria
Time Frame:From randomization to the first occurrence of disease progression as determined by an independent review committee (IRC) or death from any cause (up to approximately 8 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:PFS as Determined by the Investigator
Time Frame:From randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years)
Safety Issue:
Description:
Measure:Complete Response Rate
Time Frame:Up to approximately 8 years
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 8 years
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From randomization to death from any cause (up to approximately 8 years)
Safety Issue:
Description:
Measure:Duration of Objective Response (DOR)
Time Frame:From the first occurrence of a documented objective response (complete response or partial response) to disease progression or death from any cause, whichever occurs first (up to approximately 8 years)
Safety Issue:
Description:
Measure:Duration of Complete Reponse (CR)
Time Frame:From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (up to approximately 8 years)
Safety Issue:
Description:
Measure:Time to Deterioration in Physical Functioning and Fatigue, as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
Time Frame:Up to approximately 8 years
Safety Issue:
Description:
Measure:Time to Deterioration in Lymphoma Symptoms, as Measured by the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)
Time Frame:Up to approximately 8 years
Safety Issue:
Description:
Measure:Percentage of Participants with Adverse Events (AEs)
Time Frame:Up to approximately 8 years
Safety Issue:
Description:
Measure:Serum Concentration of M + Len
Time Frame:Up to approximately 8 years
Safety Issue:
Description:
Measure:Area Under the Curve (AUC) of M + Len
Time Frame:Up to approximately 8 years
Safety Issue:
Description:
Measure:Percentage of Participants with Anti-Drug Antibodies (ADAs)
Time Frame:Up to approximately 8 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

July 6, 2021