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
Phase 1
Active, not recruiting
- Conditions
- Diffuse Large B-cell Lymphoma
- Interventions
- Registration Number
- NCT03677154
- Lead Sponsor
- 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 188
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Consolidation Therapy (Cohort A) Mosunetuzumab Intravenous (IV) Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD). Elderly/Unfit Previously Untreated Monotherapy (Cohort B) Mosunetuzumab Intravenous (IV) Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D). Elderly/Unfit Previously Untreated Combination Therapy (Cohort C) Mosunetuzumab Subcutaneous (SC) Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin. Elderly/Unfit Previously Untreated Combination Therapy (Cohort C) Polatuzumab Vedotin Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin. Elderly/Unfit Previously Untreated Combination Therapy (Cohort C) Tocilizumab Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab in combination with polatuzumab vedotin. Consolidation Therapy (Cohort A) Tocilizumab Participants with a partial response to first-line chemotherapy will receive mosunetuzumab up to the recommended consolidation dose (RCD). Elderly/Unfit Previously Untreated Monotherapy (Cohort B) Tocilizumab Elderly/unfit participants with previously untreated DLBCL will receive mosunetuzumab at the previously determined recommended phase II dose (RP2D).
- Primary Outcome Measures
Name Time Method Percentage of Participants with Adverse Events 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 (Cohort A) 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) PET-CT Objective Response Rate (ORR) at PRA According to Lugano 2014 Response Criteria as Determined by the Investigator (Cohort B) 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) PET-CT ORR at PRA According to the Lugano 2014 Criteria as Determined by an Independent Review Committee (IRC) (Cohort C) 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days)
- Secondary Outcome Measures
Name Time Method Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC QLQ-C30 (Cohorts B and C) 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) Maximum Serum Concentration (Cmax) of Mosunetuzumab SC 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 SC 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 SC 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 IV At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) Maximum Serum Concentration (Cmax) of Mosunetuzumab IV 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 IV At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) Maximum Serum Concentration (Cmax) of Polatuzumab Vedotin IV 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 Polatuzumab Vedotin IV At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) End of Infusion Concentration (Ceoi) of Polatuzumab Vedotin IV At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) Overall Survival (OS) From the first study treatment to death from any cause 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) 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 (Cohorts B and C) 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) Area Under the Curve (AUC) of Mosunetuzumab IV 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 IV At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) Time to Maximum Serum Concentration (Tmax) of Mosunetuzumab SC 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 SC At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) Clearance (CL) of Polatuzumab Vedotin IV At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) Trough Concentration (Ctrough) of Polatuzumab Vedotin IV At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) Duration of Response (DOR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) From the first occurrence of a documented objective response to disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years) Duration of Confirmed Response (DOCR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) From the first occurrence of a documented CR to disease progression or relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years) Clearance (CL) of Mosunetuzumab SC 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 Polatuzumab Vedotin IV At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) PET-CT Rate According to the Lugano 2014 Criteria at PRA as Determined by the Investigator (Cohorts B and C) and IRC (Cohort C) 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) 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 (Cohorts A and C) Baseline through 2 years after PRA (up to a total of approximately 2.5 years) 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) Baseline through 2 years after PRA (up to a total of approximately 2.5 years) Anti-Drug Antibodies (ADAs) to Mosunetuzumab 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 Polatuzumab Vedotin IV 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 the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale (Cohorts B and C) 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) Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC IL17 (Cohorts B and C) 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 Polatuzumab Vedotin (Cohort C) At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) Progression-Free Survival (PFS) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) From the first study treatment to the first occurrence of disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years)
Trial Locations
- Locations (27)
Rambam Medical Center
🇮🇱Haifa, Israel
Carmel medical center
🇮🇱Haifa, Israel
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
Fort Wayne Medical Institute
🇺🇸Fort Wayne, Indiana, United States
University of Alabama at Birmingham School of Medicine
🇺🇸Birmingham, Alabama, United States
University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica
🇺🇸Santa Monica, California, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Soroka Medical Center
🇮🇱Beer Sheva, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Hadassah Ein-Karem
🇮🇱Jerusalem, Israel
Meir Medical Center
🇮🇱Kfar- Saba, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Yeouido St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
PRATIA MCM Kraków
🇵🇱Kraków, Poland
Hospital Universitario Virgen Macarena
🇪🇸Seville, Sevilla, Spain
Hospital Universitario Vall d Hebron
🇪🇸Barcelona, Spain
Institut Catala d Oncologia Hospitalet
🇪🇸Barcelona, Spain
Hospital San Pedro de Alcantara
🇪🇸Caceres, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan