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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

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ClinicalTrials.gov Identifier: NCT03677154
Recruitment Status : Recruiting
First Posted : September 19, 2018
Last Update Posted : September 10, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE September 11, 2018
First Posted Date  ICMJE September 19, 2018
Last Update Posted Date September 10, 2020
Actual Study Start Date  ICMJE May 23, 2019
Estimated Primary Completion Date April 19, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline through approximately 90 days after last study treatment ]
  • Positron Emission Tomography-Computed Tomography (PET-CT) Complete Response (CR) Rate at Time of Primary Response Assessment (PRA) According to Lugano 2014 Response Criteria [ Time Frame: 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2020)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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 [ 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) ]
  • Time to Deterioration in European Organization for Research and Treatment of Cancer Item Library (EORTC-IL17) Physical Functioning [ 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) ]
  • Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale [ 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B-cell Lymphoma
Intervention  ICMJE
  • Drug: Mosunetuzumab
    Participants will receive intravenous (IV) mosunetuzumab.
  • Drug: Tocilizumab
    Participants will receive tocilizumab via IV as needed to manage severe cytokine release syndrome (CRS).
Study Arms  ICMJE
  • Experimental: Consolidation Therapy Dose-Finding
    Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).
    Interventions:
    • Drug: Mosunetuzumab
    • Drug: Tocilizumab
  • Experimental: Consolidation Therapy Expansion Cohort
    Participants with a partial response to first-line chemotherapy will receive mosunetuzumab at the recommended consolidation dose (RCD) determined in the dose-finding stage.
    Interventions:
    • Drug: Mosunetuzumab
    • Drug: Tocilizumab
  • Experimental: Previously Untreated DLBCL Safety Cohort
    Participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).
    Interventions:
    • Drug: Mosunetuzumab
    • Drug: Tocilizumab
  • Experimental: Previously Untreated DLBCL
    Participants with previously untreated DLBCL will receive mosunetuzumab up to the dose confirmed by the safety cohort.
    Interventions:
    • Drug: Mosunetuzumab
    • Drug: Tocilizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 21, 2020)
92
Original Estimated Enrollment  ICMJE
 (submitted: September 17, 2018)
40
Estimated Study Completion Date  ICMJE April 19, 2023
Estimated Primary Completion Date April 19, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

  • Age >/= 80 years, or age 60-79 years 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, or liver function such that the participant is unable to tolerate full dose immunochemotherapy, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)
  • 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
  • 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 macrophage activation system (MAS)/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 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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: GO40554 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com
Listed Location Countries  ICMJE Israel,   Poland,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03677154
Other Study ID Numbers  ICMJE GO40554
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP