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A Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Participants With Diffuse Large B-Cell Lymphoma Following First-Line Immunochemotherapy and as Therapy in Participants With Previously Untreated Diffuse Large B-Cell Lymphoma Who Are Unable to Tolerate Full-Dose Chemotherapy

NCT03677154

Description:

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of partial response, or in participants with previously untreated DLBCL who are unable to tolerate full-dose, first-line immunochemotherapy.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Participants With Diffuse Large B-Cell Lymphoma Following First-Line Immunochemotherapy and as Therapy in Participants With Previously Untreated Diffuse Large B-Cell Lymphoma Who Are Unable to Tolerate Full-Dose Chemotherapy
  • Official Title: A Phase I/II Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Patients With Diffuse Large B-Cell Lymphoma Following First-Line Immunochemotherapy and as Therapy in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma Who Are Unable to Tolerate Full-Dose Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: GO40554
  • NCT ID: NCT03677154

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
MosunetuzumabConsolidation Therapy Dose-Finding
TocilizumabConsolidation Therapy Dose-Finding

Purpose

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of partial response, or in participants with previously untreated DLBCL who are unable to tolerate full-dose, first-line immunochemotherapy.

Trial Arms

NameTypeDescriptionInterventions
Consolidation Therapy Dose-FindingExperimentalParticipants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).
  • Mosunetuzumab
  • Tocilizumab
Consolidation Therapy Expansion CohortExperimentalParticipants with a partial response to first-line chemotherapy will receive mosunetuzumab at the recommended consolidation dose (RCD) determined in the dose-finding stage.
  • Mosunetuzumab
  • Tocilizumab
Previously Untreated DLBCL Safety CohortExperimentalParticipants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).
  • Mosunetuzumab
  • Tocilizumab
Previously Untreated DLBCLExperimentalParticipants with previously untreated DLBCL will receive mosunetuzumab up to the dose confirmed by the safety cohort.
  • Mosunetuzumab
  • Tocilizumab

Eligibility Criteria

        Inclusion Criteria for All Cohorts

          -  At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its
             longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as >
             1.0 cm in its longest diameter

          -  Adequate hematologic function

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

        Inclusion Criteria Specific to Cohort A

        Participants in Cohort A must also meet the following criteria for study entry:

          -  Histologically confirmed DLBCL according to World Health Organization (WHO) 2016
             expected to express the cluster of differentiation-20 (CD20) antigen

          -  Best response of PR to prior systemic chemotherapy at the end of induction treatment
             in accordance with Lugano 2014 Response Criteria

        Inclusion Criteria Specific to Cohort B

        Participants in Cohort B must also meet the following criteria for study entry:

        - Previously untreated, histologically confirmed, DLBCL according to WHO 2016
        classification

        Exclusion Criteria for All Cohorts

        Participants who meet any of the following criteria will be excluded from study entry:

          -  Transformed lymphoma

          -  Prior treatment with mosunetuzumab

          -  Prior stem cell transplant (autologous and allogeneic)

          -  History of confirmed progressive multifocal leukoencephalopathy (PML)

          -  Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C
             (HCV), or Human Immunodeficiency Virus (HIV)

          -  Prior solid organ transplantation

          -  Current or past history of central nervous system (CNS) disease, such as stroke,
             epilepsy, CNS vasculitis, or neurodegenerative disease

          -  Clinically significant history of liver disease

          -  Prior treatment with radiotherapy within 2 weeks prior to Cycle 1, Day 1 (C1D1)

          -  Significant cardiovascular disease

        Exclusion Criteria Specific to Cohort A

        Participants in Cohort A who meet the following criteria will be excluded from study entry:

        - Prior treatment with chemotherapy, immunotherapy, or biologic therapy 4 weeks prior to
        C1D1

        Exclusion Criterion Specific to Cohort B

        Participants in Cohort B who meet the following criterion will be excluded from study
        entry:

        - Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events
Time Frame:Baseline through approximately 90 days after last study treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maximum Serum Concentration (Cmax) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Minimum Serum Concentration (Cmin) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Area Under the Curve (AUC) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Clearance (CL) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Volume of Distribution at Steady State (Vss) of Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Objective Response Rate (ORR), Defined as Complete Response (CR) or Partial Response (PR) at Time of PRA Based on PET-CT as Assessed According to Lugano 2014 Response Criteria
Time Frame:Baseline through 2 years after PRA (up to a total of approximately 2.5 years)
Safety Issue:
Description:
Measure:Best ORR (CR or PR at any time) on Study Based on PET-CT and/or CT scans as Assessed According to Lugano 2014 Response Criteria
Time Frame:Baseline through 2 years after PRA (up to a total of approximately 2.5 years)
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:From the first occurrence of a documented objective response to disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS)
Time Frame:From the first study treatment to the first occurrence of disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Event-Free Survival (EFS)
Time Frame:From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Anti-Drug Antibodies (ADAs) to Mosunetuzumab
Time Frame:At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

February 21, 2020