NCT04205838

Anakinra in Preventing Severe Chimeric Antigen Receptor T-Cell Related Encephalopathy Syndrome in Patients With Recurrent or Refractory Large B-cell Lymphoma

IL-1 Receptor Antagonist to Prevent Severe Chimeric Antigen Receptor T-Cell Related Encephalopathy Syndrome

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well anakinra works in preventing severe chimeric antigen receptor T-cell-related encephalopathy syndrome after chimeric antigen receptor T-cell therapy in patients with large B-cell lymphoma that has come back or has not responded to treatment. Immunosuppressive therapy, such as anakinra, is used to decrease the body?s immune response, which may prevent severe chimeric antigen receptor T-cell-related encephalopathy syndrome.

Detailed description

PRIMARY OBJECTIVES: I. To determine if it is feasible to accrue a sufficient number of study participants at one site, in order to justify expanding the trial to three additional sites (pilot study). II. To estimate the efficacy of anakinra in prevention of severe immune effector cell-associated neurotoxicity syndrome. syndrome (ICANS) (full study). SECONDARY OBJECTIVES: I. To estimate the impact that anakinra has on the efficacy of chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory lymphoma. II. To estimate the rate of subsequent ICANS development in patients who receive anakinra for grade \>= 3 cytokine release syndrome (CRS) in the absence of ICANS. III. To estimate the duration of neurotoxicity in patients who receive anakinra. IV. To estimate the duration of severe neurotoxicity in patients who receive anakinra. V. To determine if anakinra causes persistent hepatotoxicity in patients receiving CAR T-cell for refractory lymphoma. VI. to evaluate the overall toxicity of anakinra in patients receiving CAR T-cell therapy for refractory lymphoma. EXPLORATORY OBJECTIVES: I. To evaluate CRS and ICANS grade by using the American Society for Blood and Marrow Transplantation (ASBMT) 2018 consensus grading for adults. II. To investigate changes in inflammatory markers including IL-1 and IL-6 in the peripheral blood during episodes of ICANS. III. To describe the electroencephalogram (EEG) changes that characterize ICANS. OUTLINE: Patients receive standard lymphodepleting therapy including fludarabine and cyclophosphamide on days -5 to -3, then receive axicabtagene ciloleucel CAR T-cell infusion. Patients with clinical evidence of ICANS of any grade, or CRS \>= grade 3 receive anakinra subcutaneously (SC) every 6-12 hours for 12-36 doses over 9 days in the absence of unacceptable toxicity. After completion of study, patients are followed up at 30, 90, and 100 days, then at 6 months.

Conditions

• Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• High Grade B-Cell Lymphoma
• Progressive Disease
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent High Grade B-Cell Lymphoma
• Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma
• Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory High Grade B-Cell Lymphoma
• Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma
• Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	Anakinra	Given SC
BIOLOGICAL	Axicabtagene Ciloleucel	Given via infusion
DRUG	Cyclophosphamide	Given via infusion
DRUG	Fludarabine	Given via infusion
DRUG	Fludarabine Phosphate	Given via infusion

Timeline

• Start date: 2020-03-04
• Primary completion: 2026-02-19
• Completion: 2026-02-19
• First posted: 2019-12-20
• Last updated: 2026-02-27

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study