A Study to Evaluate the Safety and Efficacy of Glofitamab in Combination With Rituximab (R) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Circulating Tumor (ct)DNA High-Risk Patients With Untreated Diffuse Large B-Cell Lymphoma
Sponsor: Hoffmann-La Roche
ClinicalTrials ID:NCT04980222
This Phase II study assesses the safety and efficacy of glofitamab with R-CHOP in ctDNA high-risk DLBCL patients. Eligible participants are untreated, CD20-positive, with specific lymphoma subtypes, ECOG 0-2, and IPI 2-5. Interventions include IV administration of glofitamab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and tocilizumab for CRS management.
Patient Parameters
| Parameter | Options |
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Program Overview
This Phase II, open-label, multicenter study will evaluate the safety, efficacy, and pharmacokinetics of glofitamab in combination with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in individuals with circulating tumor DNA (ctDNA) high-risk diffuse large B-cell lymphoma (DLBCL), as the first line of treatment.
Eligibility Criteria
Inclusion Criteria
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Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses made according to the 2016 World Health Organization (WHO) classification of lymphoid neoplasms
- DLBCL, not otherwise specified, including GCB and ABC/non-GCB types as well as double-expressor lymphoma (coexpression of MYC and BCL2)
- High-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 translocations
- Patients with de novo transformed follicular lymphoma (patients with discordant bone marrow involvement, i.e., evidence of low-grade histology in bone marrow) may be considered after discussion with the Medical Monitor
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Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
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International Prognostic Index (IPI): 2-5
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Life expectancy of at least 6 months
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Adequate biomarker blood samples prior to initiation of R-CHOP on Day 1 of Cycle 1 and on Day 1 of Cycle 2 submitted for screening for determination of ctDNA status
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At least one bi-dimensionally fluorodeoxyglucose (FDG)-avid measurable lymphoma lesion on positron emission tomography/computed tomography (PET/CT) scan
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Left ventricular ejection fraction (LVEF) >=50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
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Adequate hematopoietic function
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Contraception use
Additional Inclusion Criterion for ctDNA High-Risk Participants:
- Plasma sample evaluated to be ctDNA high risk
Exclusion Criteria
- Current diagnosis of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma (gray-zone lymphoma), primary mediastinal (thymic) large B-cell lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, Burkitt lymphoma, central nervous system (CNS) lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL
- Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines, history of severe allergic or anaphylactic reactions to murine monoclonal antibodies, or known sensitivity or allergy to murine products
- Prior treatment for indolent lymphoma
- Prior solid organ or allogeneic stem cell transplant
- Prior therapy for DLBCL and high-grade B-cell lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the final dose of R-CHOP, 3 months after the final dose of tocilizumab (if applicable), or 2 months after the final dose of glofitamab
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| City of Hope Comprehensive Cancer Center | 91010 | Duarte | California |
| Stanford Cancer Center | 94305-5820 | Stanford | California |
| University of Iowa | 52242 | Iowa City | Iowa |
| Washington University; Wash Uni. Sch. Of Med | 63110 | St Louis | Missouri |
| Memorial Sloan Kettering Bergen | 07645 | Montvale | New Jersey |
| Memorial Sloan Kettering Cancer Center at Westchester | 10604 | Harrison | New York |
| Memorial Sloan Kettering Cancer Center | 10065 | New York | New York |
| Baylor University Medical Center | 75204 | Dallas | Texas |
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