An Open-Label Study Comparing Glofitamab and Polatuzumab Vedotin + Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma

NCT06047080
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Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
1,130
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Lead sponsor
Hoffmann-La Roche
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Start date
2023-09-18
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Number of sites
229
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Summary
The purpose of this study is to compare the efficacy and safety of glofitamab in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs Pola-R-CHP in participants with previously untreated CD20-positive large B-cell lymphoma (LBCL).
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Short title
An Open-Label Study Comparing Glofitamab and Polatuzumab Vedotin + Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma
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Official title
A Phase III, Multicenter, Randomized, Open-Label Study Comparing the Efficacy and Safety of Glofitamab (RO7082859) in Combination With Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) Versus Pola-R-CHP in Previously Untreated Patients With Large B-Cell Lymphoma
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2030-10-30
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First posted
2023-09-21
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Registry last updated
2026-06-15
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Primary completion date
2027-10-01
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Start date
2023-09-18
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Actual participants
1,130
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Participants
1,130
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Participant count basis
Actual
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Protocol amendments
4
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Number of sites
229
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Hoffmann-La Roche
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06047080
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ClinicalTrials.gov ID
NCT06047080
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Progression-free survival (PFS) as determined by Independent Review Facility (IRF)

    Timeframe: From randomization to the first occurrence of disease progression or relapse, or death due to any cause, whichever occurs first (up to approximately 65 months)

  1. PFS as determined by the investigator

    Timeframe: From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 65 months)

  2. PFS as determined by the investigator and IRF for participants with international prognostic index (IPI) 3-5

    Timeframe: From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to 65 months)

  3. Event-free survival efficacy causes (EFSeff)

    Timeframe: From randomization to the earliest occurrence of disease progression or relapse; death due to any cause; initiation of new anti-lymphoma treatment; or positive biopsy for residual disease after treatment completion (up to approximately 65 months)

  4. Complete response (CR) rate

    Timeframe: At the end of treatment (up to approximately 65 months)

  5. Objective response rate (ORR)

    Timeframe: At treatment completion or discontinuation (up to approximately 65 months)

  6. Overall survival (OS)

    Timeframe: From randomization to death from any cause (up to approximately 65 months)

  7. Duration of response (DOR)

    Timeframe: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 65 months)

  8. Duration of complete response (DOCR)

    Timeframe: From the first occurrence of a documented complete response (CR) to disease progression or death, whichever occurs first (up to approximately 65 months)

  9. Disease-free survival (DFS)

    Timeframe: From a documented CR at the end of treatment to disease progression or death, whichever occurs first (up to approximately 65 months)

  10. Serum concentration of glofitamab

    Timeframe: Up to approximately 65 months

  11. Incidence of anti-drug antibodies (ADAs)

    Timeframe: Baseline up to approximately 65 months

  12. Proportion of participants experiencing a clinically meaningful improvement in physical functioning and fatigue (EORTC QLQ-C30) and lymphoma symptoms (FACT-Lym LymS)

    Timeframe: Up to approximately 65 months

  13. Time to deterioration in physical functioning and fatigue (EORTC QLQ-C30) and lymphoma symptoms (FACT-Lym LymS)

    Timeframe: Up to approximately 65 months

  14. Percentage of Participants with Adverse Events (AEs)

    Timeframe: From randomization to the end of study (up to approximately 65 months)

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
80 Years
Healthy volunteers
No

  • Previously untreated participants with CD20-positive LBCL
  • Ability to provide tumor tissue
  • International prognostic index (IPI) score 2-5
  • Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2
  • At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or MRI
  • Left ventricular ejection fraction (LVEF) >/=50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
  • Adequate hematologic function
  • Negative HIV test at screening with exceptions as defined by the protocol
  • Negative SARS-CoV-2 antigen or PCR test

  • Contraindication to any of the individual components of Pola-R-CHP or glofitamab, including prior receipt of anthracyclines, or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products
  • Prior solid organ transplantation
  • Participants receiving systemic immunosuppressive agent such as, but not limited to cyclosporin, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 4 weeks prior to first dose of study treatment
  • Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
  • History of indolent lymphoma (e.g., Follicular Lymphoma, Marginal Zone Lymphoma, Waldenstrom macroglobulinemia)
  • Current diagnosis of the following: Follicular lymphoma grade 3B; transformations of indolent B-cell lymphomas (e.g., de novo transformed follicular lymphoma); mediastinal grey zone lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; primary large B-cell lymphoma of immune-privileged sites (encompassing primary diffuse large B-cell lymphoma of the CNS, primary large B-cell lymphoma of the vitreoretina and primary large B-cell lymphoma of the testis); primary effusion DLBCL; and primary cutaneous DLBCL, leg type
  • Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma
  • Prior treatment with systemic immunotherapeutic agents
  • Prior use of any monoclonal antibody for the purposes of treating cancer within 3 months of the start of Cycle 1
  • Any investigational therapy for the purposes of treating cancer within 28 days prior to the start of Cycle 1
  • Prior radiotherapy to the mediastinal/pericardial region
  • Prior therapy for LBCL, with the exception of corticosteriods
  • Corticosteroid use > 30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control
  • History of other malignant or non-malignant diseases that could affect compliance with the protocol or interpretation of results
  • Significant or extensive history of cardiovascular disease
  • Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
  • Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
  • Known or suspected chronic active Epstein-Barr viral infection
  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
  • Active autoimmune disease requiring treatment
  • Clinically significant liver disease
  • Live, attenuated vaccine within 4 weeks before study treatment infusion on Day 1 of Cycle 1 or anticipation that such a live, attenuated vaccine will be required during the study. Live vaccines during the study and until participants B cells recover are prohibited
  • Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety
  • Suspected active or latent tuberculosis
  • Positive test results for chronic hepatitis B infection, hepatitis C, or the human T-lymphotropic virus type 1 (HTLV-1)
  • History of progressive multifocal leukoencephalopathy
Sources for eligibility
clinicaltrials.gov

  • Alaska Oncology & Hematology, LLCAnchorage, United States
  • Kaiser Permanente - Anaheim (E. La Palma)Anaheim, United States
  • University of California, San Francisco-FresnoClovis, United States
  • City of Hope National Medical CenterDuarte, United States
  • City of Hope - Lennar Foundation Cancer CenterIrvine, United States
  • Valkyrie Clinical TrialsLos Angeles, United States
  • UCLA Jonsson Comprehensive Cancer CenterLos Angeles, United States
  • Kaiser Permanente - RosevilleRoseville, United States
  • Kaiser Permanente - Santa ClaraSanta Clara, United States
  • Stanford Univ School of MedStanford, United States
  • Kaiser Permanente Medical CtrVallejo, United States
  • University of Colorado Cancer CenterAurora, United States
  • Rocky Mountain Cancer Center - DenverLittleton, United States
  • Yale University School Of MedicineNew Haven, United States
  • Medstar Franklin Square Medical CenterWashington D.C., United States
  • Miami Cancer Institute of Baptist Health, Inc.Miami, United States
  • Memorial Cancer Institute at Memorial WestPembroke Pines, United States
  • Hawaii Cancer CareHonolulu, United States
  • Robert H. Lurie Comprehensive Cancer Center of Northwestern UniversityChicago, United States
  • Illinois Cancer CarePeoria, United States
  • Springfield ClinicSpringfield, United States
  • University of IowaIowa City, United States
  • Ascension Via Christi ResearchWichita, United States
  • Ochsner Medical CenterNew Orleans, United States
  • Massachusetts General HospitalBoston, United States

And 204 more, listed on the interactive page.

Sources for sites
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