NCT05873712

Zanubrutinib and Lisocabtagene Maraleucel for the Treatment of Richter's Syndrome

A Phase II Study Evaluating the Safety and Efficacy of the Combination of Zanubrutinib Plus Lisocabtagene Maraleucel for Richter's Syndrome

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Aseel Alsouqi · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well zanubrutinib and lisocabtagene maraleucel (liso-cel) work together in treating patients with Richter's syndrome that has come back (recurrent) or does not respond to treatment (refractory). Richter's syndrome occurs when chronic lymphocytic leukemia and/or small lymphocytic leukemia transforms into an aggressive lymphoma, which is a cancer of the lymph nodes. Zanubrutinib is a class of medication called a kinase inhibitor. These drugs work by preventing the action of abnormal proteins that tell cancer cells to multiply, which helps stop the spread of cancer. Liso-cel is a type of treatment known as chimeric antigen receptor (CAR) T cell therapy. CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving zanubrutinib and liso-cell together may kill more cancer cells in patients with recurrent or refractory Richter's syndrome.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the efficacy of the combination of zanubrutinib and lisocabtagene maraleucel (liso-cel) for the treatment of Richter's syndrome (RS). SECONDARY OBJECTIVES: I. To describe the safety profile of the combination of zanubrutinib and liso-cel for RS. II. To evaluate duration of the efficacy of the combination of zanubrutinib and liso-cel for RS CORRELATIVE OBJECTIVES: I. Describe T-cell subsets before and after zanubrutinib initiation, as well as post liso-cel infusion. II. To describe the persistence of liso-cel. III. To describe the tumor microenvironment post liso-cel infusion at relapse. IV. Investigate the correlation between inflammatory cytokines and measures of inflammation and outcomes and rates of adverse events including cytokine release syndrome (CRS). V. Investigate chronic lymphocytic leukemia (CLL) persistence post treatment. OUTLINE: Patients receive zanubrutinib orally (PO) twice daily (BID) for up to day 90 and undergo leukaphereis at least 14 days after starting zanubrutinib. Patients receive fludarabine intravenously (IV) and cyclophosphamide IV on days -5 to -3 and liso-cel IV over 5-30 minutes on day 0. Patients also undergo bone marrow (BM) biopsy and lymph node biopsy at screening and follow up, and undergo collection of blood samples and computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI) throughout the trial. After study completion, patients are followed for 24 months, and then every 6 months until disease progression or death.

Conditions

• Recurrent Transformed Chronic Lymphocytic Leukemia
• Refractory Transformed Chronic Lymphocytic Leukemia
• Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma
• Recurrent Transformed B-Cell Non-Hodgkin Lymphoma
• Recurrent Transformed Non-Hodgkin Lymphoma
• Refractory Transformed Non-Hodgkin Lymphoma
• Refractory Transformed B-cell Non-Hodgkin Lymphoma
• Refractory Transformed

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Bone Marrow Biopsy	Undergo BM biopsy
PROCEDURE	Computed Tomography	Undergo CT and/or PET/CT
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
PROCEDURE	Leukapheresis	Given IV
BIOLOGICAL	Lisocabtagene Maraleucel	Given IV
PROCEDURE	Lymph Node Biopsy	Undergo lymph node biopsy
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
DRUG	Zanubrutinib	Given PO

Timeline

• Start date: 2023-07-28
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2023-05-24
• Last updated: 2026-03-03

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study