Clinical Trials /

A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab + Lenalidomide, RO7082859 + Lenalidomide, and RO7082859 + Lenalidomide + Obinutuzumab in Participants With Relapsed or Refractory Follicular Lymphoma

NCT04246086

Description:

This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of mosunetuzumab + lenalidomide, RO7082859 + lenalidomide, and RO7082859 + lenalidomide + obinutuzumab in participants with relapsed or refractory (R/R) follicular lymphoma (FL).

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab + Lenalidomide, RO7082859 + Lenalidomide, and RO7082859 + Lenalidomide + Obinutuzumab in Participants With Relapsed or Refractory Follicular Lymphoma
  • Official Title: A Phase Ib, Open-Label, Non-Randomized, Multicenter Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab in Combination With Lenalidomide or RO7082859 in Combination With Lenalidomide or RO7082859 in Combination With Obinutuzumab Plus Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: CO41942
  • SECONDARY ID: 2019-004291-20
  • NCT ID: NCT04246086

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
CD20-TCBRO7082859CD20-TCB + Lenalidomide
MosunetuzumabRO7030816Mosunetuzumab + Lenalidomide
ObinutuzumabRO5072759CD20-TCB + Lenalidomide
TocilizumabRO4877533CD20-TCB + Lenalidomide
LenalidomideCD20-TCB + Lenalidomide

Purpose

This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of mosunetuzumab + lenalidomide, RO7082859 + lenalidomide, and RO7082859 + lenalidomide + obinutuzumab in participants with relapsed or refractory (R/R) follicular lymphoma (FL).

Trial Arms

NameTypeDescriptionInterventions
Mosunetuzumab + LenalidomideExperimentalParticipants will receive treatment with mosunetuzumab for 8-12 cycles, plus lenalidomide for up to 12 total cycles (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)
  • Mosunetuzumab
  • Tocilizumab
  • Lenalidomide
CD20-TCB + LenalidomideExperimentalParticipants will receive obinutuzumab pretreatment, followed by treatment with CD20-TCB for 8-12 cycles, plus lanalidomide for up to 12 total cycles (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)
  • CD20-TCB
  • Obinutuzumab
  • Tocilizumab
  • Lenalidomide
CD20-TCB + Obinutuzumab + LenalidomideExperimentalParticipants will receive obinutuzumab pretreatment, followed by treatment with CD20-TCB and obinutuzumab for 8-12 cycles, plus lenalidomide for up to 12 cycles (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)
  • CD20-TCB
  • Obinutuzumab
  • Tocilizumab
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria

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

          -  R/R FL after treatment with at least one prior chemo immunotherapy regimen that
             included an anti CD20 monoclonal antibody (MAb) and for which no other more
             appropriate treatment option exists as determined by the investigator

          -  Histologically documented lymphoma that expresses CD20 at time of diagnosis as
             determined by the local laboratory

          -  Fluorodeoxyglucose avid lymphoma (i.e., positron emission tomography (PET) positive
             lymphoma)

          -  At least one bi dimensionally measurable nodal lesion (>1.5 cm in its largest
             dimension by PET- computed tomography (CT) scan), or at least one bi dimensionally
             measurable extranodal lesion (>1.0 cm in its largest dimension by PET-CT scan)

          -  Availability of a representative tumor specimen and the corresponding pathology report
             for confirmation of the diagnosis of FL

          -  Agreement to comply with all local requirements of the Len risk minimization plan

          -  For women of childbearing potential: agreement to remain abstinent 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,
             and for at least 12 months after the final dose of CD20 TCB, 28 days after the last
             dose of Len, 18 months after the last dose of G, 3 months after the final dose of
             tocilizumab, and 3 months after the final dose of Mosun. Women must refrain from
             donating eggs during this same period

          -  For men: agreement to remain abstinent or use contraceptive measures and agreement to
             refrain from donating sperm, 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 2 months after the final dose of CD20-TCB, 28 days
             after last dose of Len, 18 months after the last dose of G, 3 months after the final
             dose of tocilizumab, and 3 months after the final dose of Mosun

        Exclusion Criteria

          -  Grade 3b FL

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

          -  Documented refractoriness to an obinutuzumab monotherapy containing regimen in
             CD20-TCB containing treatment combination

          -  Active or history of central nervous system lymphoma or leptomeningeal infiltration

          -  Prior standard or investigational anti-cancer therapy as specified

          -  Clinically significant toxicity (other than alopecia) from prior treatment that has
             not resolved to Grade <=2 prior to Day 1 of Cycle 1

          -  Treatment with systemic immunosuppressive medications, including, but not limited to,
             prednisone, 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
             MAbs

          -  Known sensitivity or allergy to murine products

          -  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
             or any component of the CD20-TCB, Mosun, G, Len, or thalidomide formulation, including
             mannitol

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

          -  Known history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis or evidence of active pneumonitis on screening chest CT scan

          -  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 infection or hemophagocytic
             syndrome

          -  Active Hepatitis B and Hepatitis C infection or autoimmune disease requiring treatment

          -  Known history of HIV positive status

          -  History of progressive multifocal leukoencephalopathy

          -  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

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

          -  Contraindication to treatment for thromboembolism prophylaxis

          -  Grade >=2 neuropathy

          -  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 or significant pulmonary disease

          -  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

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

          -  Inadequate hematologic function

          -  Any of the following abnormal laboratory values

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

          -  Life expectancy < 3 months

          -  Unable to comply with the study protocol, in the investigator's judgment

          -  History of illicit drug or alcohol abuse within 12 months prior to screening, in the
             investigator's judgment

          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the
             investigator's or Medical Monitor'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:Dose-Limiting Toxicities (DLTs)
Time Frame:Cycle 2 Days 2-21 (cycle length = 28 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Complete Response Rate (CRR)
Time Frame:Up to the end of Cycle 8 (cycle length = 28 days)
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:Up to the end of Cycle 8 (cycle length = 28 days)
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, up to the end of Cycle 8 (cycle length = 28 days)
Safety Issue:
Description:
Measure:Duration of Complete Reponse (DOCR)
Time Frame:From the first occurrence of a documented complete response (CR) to disease progression, relapse, or death from any cause, whichever occurs first, up to the end of Cycle 8 (cycle length = 28 days)
Safety Issue:
Description:
Measure:Minimum Serum Concentration (Cmin) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Safety Issue:
Description:
Measure:Maximum Serum Concentration (Cmax) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Safety Issue:
Description:
Measure:Area Under the Concentration vs Time Curve (AUC) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Safety Issue:
Description:
Measure:Cmin of CD20-TCB
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Safety Issue:
Description:
Measure:Cmax of CD20-TCB
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Safety Issue:
Description:
Measure:AUC of CD20-TCB
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment)
Safety Issue:
Description:
Measure:Percentage of Participants with Anti-Drug Antibodies (ADAs) to CD20-TCB
Time Frame:At pre-defined intervals from baseline through follow-up (2 years after last treatment)
Safety Issue:
Description:
Measure:Percentage of Participants with ADAs to Mosunetuzumab
Time Frame:At pre-defined intervals from baseline through follow-up (2 years after last treatment)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

March 25, 2020