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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

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: NCT03677141
Recruitment Status : Recruiting
First Posted : September 19, 2018
Last Update Posted : October 23, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : June 22, 2022
Estimated Study Completion Date : June 22, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Phase Ib: Mosunetuzumab (M)-CHOP Dose Finding
Participants will receive M-CHOP up to the phase II recommended dose (RP2D).
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.

Experimental: Phase Ib: M-CHP-Pola Dose-Finding
Participants will receive M-CHP-Pola up to the RP2D.
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.

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.
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.

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.
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.

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.
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.

Experimental: Phase II: M-CHOP 1L DLBCL
Participants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage.
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 :
  1. Percentage of Participants with Adverse Events (AE) [ Time Frame: Baseline through approximately 90 days after the last study treatment ]
  2. 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 :
  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. 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) ]
  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]
  13. 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) ]
  14. 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) ]
  15. 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) ]
  16. PFS at 1 Year [ Time Frame: Randomization to 1 Year ]
  17. 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) ]
  18. 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) ]
  19. 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

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.


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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


Contacts
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Contact: Reference Study ID Number: GO40515 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
Show Show 31 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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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: October 23, 2020
Last Verified: October 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).

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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
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
Hormones, Hormone Substitutes, and Hormone Antagonists