Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Drug: Mosunetuzumab Drug: Tocilizumab Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 23, 2019
Estimated Primary Completion Date : April 19, 2023
Estimated Study Completion Date : April 19, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Consolidation Therapy Dose-Finding
Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD).
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).

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.
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).

Experimental: Previously Untreated DLBCL Safety Cohort
Participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).
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).

Experimental: Previously Untreated DLBCL
Participants with previously untreated DLBCL will receive mosunetuzumab up to the dose confirmed by the safety cohort.
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).




Primary Outcome Measures :
  1. Percentage of Participants with Adverse Events [ Time Frame: Baseline through approximately 90 days after last study treatment ]
  2. 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) ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]
  13. 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) ]
  14. 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  • 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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03677154


Contacts
Layout table for location contacts
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

Locations
Show Show 33 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03677154    
Other Study ID Numbers: GO40554
First Posted: September 19, 2018    Key Record Dates
Last Update Posted: September 10, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
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).

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin