Clinical Trials /

Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Participants With Diffuse Large B-Cell Lymphoma Following First-Line Immunochemotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Participants With Previously Untreated Diffuse Large B-Cell Lymphoma

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 stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Participants With Diffuse Large B-Cell Lymphoma Following First-Line Immunochemotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Participants With Previously Untreated Diffuse Large B-Cell Lymphoma
  • Official Title: A Phase I/II Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Patients With Diffuse Large B-Cell Lymphoma Following First-Line Immunotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Patients With Previously Untreated Diffuse Large B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: GO40554
  • NCT ID: NCT03677154

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
Mosunetuzumab Intravenous (IV)Consolidation Therapy (Cohort A)
Mosunetuzumab Subcutaneous (SC)Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)
Polatuzumab VedotinElderly/Unfit Previously Untreated Combination Therapy (Cohort C)
TocilizumabConsolidation Therapy (Cohort A)

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 stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.

Trial Arms

NameTypeDescriptionInterventions
Consolidation Therapy (Cohort A)ExperimentalParticipants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).
  • Mosunetuzumab Intravenous (IV)
  • Tocilizumab
Elderly/Unfit Previously Untreated Monotherapy (Cohort B)ExperimentalElderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).
  • Mosunetuzumab Intravenous (IV)
  • Tocilizumab
Elderly/Unfit Previously Untreated Combination Therapy (Cohort C)ExperimentalElderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin.
  • Mosunetuzumab Subcutaneous (SC)
  • Polatuzumab Vedotin
  • 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

          -  One prior therapy with any systemic anthracycline-based chemoimmunotherapy containing
             regimen for previously untreated DLBCL

          -  Best response of SD or PR to prior systemic chemoimmunotherapy at the end of induction
             treatment in accordance with the Lugano 2014 criteria

        Inclusion Criteria Specific to Cohorts B and C

        Participants in Cohorts B and C must also meet the following criteria for study entry:

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

          -  Age >/= 80 years, or

          -  Age 60-79 years and considered ineligible for chemoimmuotherapy (R-CHOP) with at least
             one of the following: Impairment in at least one activity of daily living as defined
             in the protocol; impairment in at least one instrumental activity of daily living as
             defined in the protocol; impairment in cardiac function, renal function, liver
             function, or other comorbidities such that the participant is unfit for full-dose
             immunochemotherapy, such as rituximab plus cyclophosphamide, doxorubicin, vincristine,
             and prednisone (R-CHOP)

        Exclusion Criteria for All Cohorts

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

          -  Transformed lymphoma

          -  CNS 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)

          -  History of hemophagocytic lymphohistiocytosis (HLH)

          -  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 Cohorts B and C

        Participants in Cohorts B and C who meet the following criterion will be excluded from
        study entry:

        - Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy

        Exclusion Criteria Specific to Cohort C

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

        - Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of
        Charcot-Marie-Tooth disease
      
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 IV
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 IV
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 IV
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 IV
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 IV
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:Maximum Serum Concentration (Cmax) of Mosunetuzumab SC
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:Time to Maximum Serum Concentration (Tmax) of Mosunetuzumab SC
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 SC
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 SC
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 SC
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 SC
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:Maximum Serum Concentration (Cmax) of Polatuzumab Vedotin IV
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 Polatuzumab Vedotin IV
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 Polatuzumab Vedotin IV
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 Polatuzumab Vedotin IV
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 Polatuzumab Vedotin IV
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:PET-CT Rate According to the Lugano 2014 Criteria at PRA as Determined by the Investigator (Cohort C)
Time Frame:6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
Safety Issue:
Description:
Measure:Objective Response Rate (ORR), Defined as the Proportion of Participants with a Complete Response (CR) or Partial Response (PR) at PRA as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)
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) During the Study Based on PET-CT and/or CT Scans as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)
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) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)
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) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C)
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:Overall Survival (OS)
Time Frame:From the first study treatment to death from any cause
Safety Issue:
Description:
Measure:Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Physical Functioning and Fatigue (Cohorts B and C)
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:Time to Deterioration in European Organization for Research and Treatment of Cancer Item Library (EORTC-IL17) Physical Functioning (Cohorts B and C)
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:Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale (Cohorts B and C)
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:Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC QLQ-C30 (Cohorts B and C)
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:Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC IL17 (Cohorts B and C)
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:
Measure:Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin (Cohort C)
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 2, 2021