A Phase Ib/II Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Participants With B-Cell Non-Hodgkin Lymphoma
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| ClinicalTrials.gov Identifier: NCT03677141 |
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Recruitment Status :
Active, not recruiting
First Posted : September 19, 2018
Last Update Posted : May 16, 2023
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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Brief Summary:
This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| B-cell Non-Hodgkin Lymphoma | Drug: Mosunetuzumab Drug: Polatuzumab Vedotin Drug: Rituxumab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Tocilizumab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 160 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase Ib/II, Open-Label, Multicenter, Randomized, Controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma |
| Actual Study Start Date : | February 8, 2019 |
| Actual Primary Completion Date : | November 18, 2022 |
| Estimated Study Completion Date : | November 30, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Lymphoma
Drug Information available for:
Polatuzumab vedotin
| Arm | Intervention/treatment |
|---|---|
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Experimental: Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
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Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab. Drug: Polatuzumab Vedotin Participants will receive polatuzumab vedotin via IV. Drug: Cyclophosphamide Participants will receive cyclophosphamide via IV. Drug: Doxorubicin Participants will receive doxorubicin via IV. Drug: Vincristine Participants will receive vincristine via IV. Drug: Prednisone Participants will receive oral prednisone. Drug: Tocilizumab Participants will receive tocilizumab via IV. |
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Experimental: Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
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Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab. Drug: Polatuzumab Vedotin Participants will receive polatuzumab vedotin via IV. Drug: Cyclophosphamide Participants will receive cyclophosphamide via IV. Drug: Doxorubicin Participants will receive doxorubicin via IV. Drug: Prednisone Participants will receive oral prednisone. Drug: Tocilizumab Participants will receive tocilizumab via IV. |
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Experimental: Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety Cohort
Participants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
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Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab. Drug: Cyclophosphamide Participants will receive cyclophosphamide via IV. Drug: Doxorubicin Participants will receive doxorubicin via IV. Drug: Vincristine Participants will receive vincristine via IV. Drug: Prednisone Participants will receive oral prednisone. Drug: Tocilizumab Participants will receive tocilizumab via IV. |
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Experimental: Phase II: M-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
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Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab. Drug: Polatuzumab Vedotin Participants will receive polatuzumab vedotin via IV. Drug: Cyclophosphamide Participants will receive cyclophosphamide via IV. Drug: Doxorubicin Participants will receive doxorubicin via IV. Drug: Prednisone Participants will receive oral prednisone. Drug: Tocilizumab Participants will receive tocilizumab via IV. |
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Active Comparator: Phase II: Rituxumab (R)-CHP-Pola 1L DLBCL
Participants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
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Drug: Polatuzumab Vedotin
Participants will receive polatuzumab vedotin via IV. Drug: Rituxumab Participants will receive rituxumab via IV. Drug: Cyclophosphamide Participants will receive cyclophosphamide via IV. Drug: Doxorubicin Participants will receive doxorubicin via IV. Drug: Prednisone Participants will receive oral prednisone. |
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Experimental: Phase II: M-CHOP 1L DLBCL
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage.
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Drug: Mosunetuzumab
Participants will receive intravenous (IV) mosunetuzumab. Drug: Cyclophosphamide Participants will receive cyclophosphamide via IV. Drug: Doxorubicin Participants will receive doxorubicin via IV. Drug: Vincristine Participants will receive vincristine via IV. Drug: Prednisone Participants will receive oral prednisone. Drug: Tocilizumab Participants will receive tocilizumab via IV. |
Primary Outcome Measures :
- Percentage of Participants with Adverse Events (AE) [ Time Frame: Baseline through approximately 90 days after the last study treatment ]
- Complete Response (CR) Rate at the Time of Primary Response Assessment Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Assessed According to Lugano 2014 Response Criteria [ Time Frame: Approximately 6-8 weeks after Cycle 6 (cycle = 21 days), or at early treatment discontinuation ]
Secondary Outcome Measures :
- 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) ]
- Maximum Plasma Concentration (Cmax) of Polatuzumab Vedotin [ Time Frame: At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) ]
- Minimum Plasma Concentration (Cmin) of Polatuzumab Vedotin [ Time Frame: At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) ]
- AUC of Polatuzumab Vedotin [ Time Frame: At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) ]
- CL of Polatuzumab Vedotin [ Time Frame: At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) ]
- Vss of Polatuzumab Vedotin [ Time Frame: At pre-defined intervals from Cycle 1, Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) ]
- Best Objective Response Rate (ORR), Defined as Complete Response (CR) or Partial Response (PR) at any Time on Study Based on PET-CT and/or CT scan as Assessed According to Lugano 2014 Response Criteria [ Time Frame: Baseline through 2 years after partial response assessment (PRA) (up to a total of approximately 2.5 years) ]
- Duration of Response (DOR) [ Time Frame: From the first occurrence of a response to disease progression, relapse, or death, whichever comes 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) ]
- ADAs to Polatuzumab Vedotin [ Time Frame: 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) [ Time Frame: From randomization to the first occurrence of disease progression, relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years) ]
- PFS at 1 Year [ Time Frame: Randomization to 1 Year ]
- Event-Free Survival (EFS) [ Time Frame: From randomization to the first occurrence of disease progression or relapse, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first (up to approximately 2.5 years) ]
- Time to Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30) Physical Functioning and Fatigue [ Time Frame: From baseline through follow-up (up to approximately 2.5 years) ]
- Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale [ Time Frame: From baseline through follow-up (up to approximately 2.5 years) ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria for Phase Ib and Phase II Portions
- 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
- Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
- Adequate hematologic function
Inclusion Criteria for Phase Ib Portion
Participants must also meet the following criteria for study entry into the Phase Ib portion:
- Histologically confirmed B-cell NHL according to the World Health Organization (WHO) 2016 classification expected to express the cluster of differentiation-20 (CD20) antigen
- Relapsed or refractory (R/R) B-cell NHL after at least one prior systemic lymphoma therapy
- Treatment with at least one prior CD20-directed therapy
- Group B only: no prior treatment with polatuzumab vedotin
Inclusion Criteria for Phase II Portion
Participants must also meet the following criteria for study entry in the Phase II portion:
- Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification
- International Prognostic Index (IPI) score of 2-5
Exclusion Criteria
- Prior treatment with mosunetuzumab
- Prior allogenic stem-cell transplant
- Current Grade >1 peripheral neuropathy
- Participants with 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
- History of autoimmune disease
- Current or past history of central nervous system (CNS) lymphoma
- Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- Significant cardiovascular disease or pulmonary disease
- Clinically significant history of liver disease
- Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis
Exclusion Criteria for Phase Ib Portion
Participants who also meet any of the following criteria will be excluded from study entry in the Phase Ib portion:
- Prior treatment with chemotherapy, immunotherapy, and biologic therapy 4 weeks prior to C1D1
- Prior treatment with radiotherapy within 2 weeks prior to C1D1
- Adverse events from prior anti-cancer therapy resolved to ≤Grade 1 (with the exception of alopecia and anorexia)
- Prior treatment with >250 mg/m^2 doxorubicin (or equivalent anthracycline dose)
Exclusion Criteria for Phase II Portion
Participants who also meet any of the following criteria will be excluded from study entry in the Phase II portion:
- Participants with transformed lymphoma
- Prior therapy for B-cell NHL
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): NCT03677141
Locations
Show 41 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT03677141 |
| Other Study ID Numbers: |
GO40515 2018-001039-29 ( EudraCT Number ) |
| First Posted: | September 19, 2018 Key Record Dates |
| Last Update Posted: | May 16, 2023 |
| Last Verified: | May 2023 |
| 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). |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Prednisone Cyclophosphamide Doxorubicin Vincristine Polatuzumab vedotin Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Anti-Inflammatory Agents Glucocorticoids Hormones |