NCT06054776

Acalabrutinib, Obinutuzumab, and Glofitamab for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

A Phase 2 Study of Glofitamab With Acalabrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies the side effects of acalabrutinib, obinutuzumab, and glofitamab and how well they work together for treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantel cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Glofitamab is a class of medications called bispecific antibodies. Bispecific antibodies are designed to simultaneously bind to T cells and cancer cell antigens, leading to T-cell activation, proliferation, and cancer cell death. Giving acalabrutinib, obinutuzumab, and glofitamab together may be a safe and effective treatment for patients with relapsed or refractory mantle cell lymphoma.

Detailed description

PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of a regimen combining acalabrutinib and glofitamab in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). (Safety Lead-In) II. Estimate the complete response (CR) rate in R/R MCL patients treated with acalabrutinib plus glofitamab. (Phase 2) SECONDARY OBJECTIVES: I. Estimate the minimal residual disease (MRD) negativity rate, time to response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and patient-reported quality of life measures (HRQOL) in R/R MCL patients treated with acalabrutinib plus glofitamab. II. Evaluate the toxicity of acalabrutinib plus glofitamab for R/R MCL. EXPLORATORY OBJECTIVES: I. Examine the prognostic value of MRD assessment by next-generation sequencing (NGS) and circulating cell-free tumor deoxyribonucleic acid (DNA) (ctDNA) assessment in patients with R/R MCL treated with acalabrutinib combined with glofitamab. II. Examine the immune reconstitution, T-cell fitness, and immunomodulatory effects in patients with R/R MCL treated with acalabrutinib combined with glofitamab. III. Examine the evolution of tumor genetic profile and microenvironment in patients with R/R MCL treated with acalabrutinib combined with glofitamab. OUTLINE: Patients receive acalabrutinib orally (PO) twice daily (BID) of each cycle, obinutuzumab intravenously (IV) on days 1 and 7 of cycle 1 only, and glofitamab IV over 2-4 hours on days 8 and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with MRD positive complete response (CR), partial response (PR), or stable disease (SD) after 12 cycles of protocol therapy may continue receiving single agent acalabrutinib per standard of care during the follow-up phase of the study. Patients also undergo a echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening, as well as positron emission tomography (PET)/computed tomography (CT) or CT, and blood specimen collection throughout the trial. Patients may also undergo bone marrow biopsies throughout the trial. Upon completion of study treatment, patients are followed up at 30 days and then every 3 months for response and bi-annually for survival, for up to 4 years from start of treatment.

Conditions

• Mantle Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Acalabrutinib	Given PO
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsies
PROCEDURE	Computed Tomography	Undergo PET/CT or CT
PROCEDURE	Echocardiography	Undergo ECHO
BIOLOGICAL	Glofitamab	Given IV
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
BIOLOGICAL	Obinutuzumab	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET/CT

Timeline

• Start date: 2024-12-02
• Primary completion: 2026-10-16
• Completion: 2026-10-16
• First posted: 2023-09-26
• Last updated: 2026-01-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study