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Active, Not Recruiting

NCT Number: NCT04980222

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Aarhus Universitetshospital Skejby, Aarhus N, Denmark

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • International Prognostic Index (IPI): 2-5
  • Life expectancy of at least 6 months
  • 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
  • At least one bi-dimensionally fluorodeoxyglucose (FDG)-avid measurable lymphoma lesion on positron emission tomography/computed tomography (PET/CT) scan
  • Left ventricular ejection fraction (LVEF) >=50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
  • Adequate hematopoietic function
  • 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

Treatment and study plan

Glofitamab

Drug

Participants will receive intravenous (IV) glofitamab as per schedule specified in the treatment arm.

Tocilizumab

Drug

Participants will receive tocilizumab as needed to manage cytokine release syndrome (CRS).

Doxorubicin

Drug

Participants will receive 50 mg/m2 body surface area of doxorubicin IV as per schedule specified in the treatment arm.

Vincristine

Drug

Participants will receive 1.4 mg/m2 body surface area of vincristine IV as per schedule specified in the treatment arm.

Prednisone

Drug

Participants will receive 100 mg of prednisone or prednisolone as per schedule specified in the treatment arm.

Rituximab

Drug

Participants will receive 375 mg/m2 body surface area of rituximab IV as per schedule specified in the treatment arm.

Cyclophosphamide

Drug

Participants will receive 750 mg/m2 body surface area of cyclophosphamide IV as per schedule specified in the treatment arm.

Primary outcomes

  1. End of Treatment Complete Response (EOT CR) Rate

    Time frame: Up to approximately 24 months

Secondary outcomes

  1. Overall Response Rate (ORR) at the EOT

    Time frame: Up to approximately 24 months

  2. Progression-free Survival (PFS)

    Time frame: Up to approximately 24 months

  3. Overall Survival (OS)

    Time frame: Up to approximately 24 months

  4. Percentage of Participants with Adverse Events (AEs)

    Time frame: Up to 90 days after the final dose of study treatment

  5. Serum Concentration of Glofitamab

    Time frame: At pre-defined intervals up to approximately 10 months

  6. Maximum Concentration (Cmax) of Glofitamab

    Time frame: At pre-defined intervals up to approximately 10 months

  7. Total Exposure (AUC) of Glofitamab

    Time frame: At pre-defined intervals up to approximately 10 months

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Phase II Study Evaluating 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

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Jul 28, 2021
Registry last updated
Feb 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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