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

NCT ID: NCT04205838

Last Updated: 2025-07-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-04
• Study Completion Date: 2027-06-30

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Prevention (anakinra, CAR T-cell therapy)

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 SC every 6-12 hours for 12-36 doses over 9 days in the absence of unacceptable toxicity.

Group Type: EXPERIMENTAL

Anakinra

Intervention Type: BIOLOGICAL

Given SC

Axicabtagene Ciloleucel

Intervention Type: BIOLOGICAL

Given via infusion

Cyclophosphamide

Intervention Type: DRUG

Given via infusion

Fludarabine

Intervention Type: DRUG

Given via infusion

Fludarabine Phosphate

Intervention Type: DRUG

Given via infusion

Interventions

Anakinra

Given SC

Intervention Type: BIOLOGICAL

Axicabtagene Ciloleucel

Given via infusion

Intervention Type: BIOLOGICAL

Cyclophosphamide

Given via infusion

Intervention Type: DRUG

Fludarabine

Given via infusion

Intervention Type: DRUG

Fludarabine Phosphate

Given via infusion

Intervention Type: DRUG

Other Intervention Names

Kinaret; Kineret; rIL-1ra; rIL1RN; KTE C19; KTE-C19; KTE-C19 CAR; Yescarta; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Fluradosa; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586

Eligibility Criteria

Inclusion Criteria

• Patients with relapsed or refractory large B-cell lymphoma that has progressed on two prior lines of therapy, who meet the indication for the Food and Drug Administration (FDA)-approved therapy axicabtagene ciloleucel
• Large B-cell lymphoma includes diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma
• The above includes patients with progressive or stable disease as the best response to the most recent treatment regimen or disease progression within 12 months after autologous hematopoietic stem cell transplantation
• Patients with central nervous system (CNS) involvement of large B-cell lymphoma that originated outside of the CNS will be included (not primary CNS lymphoma)
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 2.5 upper limit of normal
• Total bilirubin =< 2.0 mg/dL
• Creatinine clearance > 30 mL/min based on Cockcroft-Gault formula
• Patients with human immunodeficiency virus (HIV) who have an undetectable viral load will be included
• Deemed competent to make medical decisions

Exclusion Criteria

• Patients who receive CAR T-cell therapy with a product other than axicabtagene ciloleucel
• Primary CNS lymphoma
• Transformed DLBCL from chronic lymphocytic leukemia (CLL)
• Burkitt?s lymphoma
• Bridging chemotherapy completed < 7 days prior to CAR T-cell lymphodepleting chemotherapy
• In patients who receive bridging chemotherapy, positron emission tomography (PET)-computed tomography (CT) or CT of chest, abdomen, pelvis was not done after bridging chemotherapy prior lympho-depleting therapy
• Most recent PET-CT or CT of all known disease is sites done more than 6 weeks prior to CAR T-cell infusion
• Any individual CNS tumor mass > 2 cm
• History of autologous hematopoietic stem cell transplantation administered less than 100 days prior to CAR T-cell infusion
• History of allogeneic hematopoietic stem cell transplantation
• Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
• Less than 3 half-lives elapsed since receiving immune checkpoint inhibitor (pembrolizumab, ipilimumab, nivolumab, atezolizumab, etc.)
• Presence of uncontrolled fungal, bacterial, or viral infection that require intravenous (IV) antimicrobial treatment
• History of autoimmune disease resulting in end-organ damage, or autoimmune disease requiring systemic immunosuppressants or disease-modifying antirheumatic drug (DMARDs) within the past 6 months
• Hypersensitivity to E. Coli-derived proteins
• Patients with HIV who have a detectable viral load
• Pregnant or nursing
• Fertile women who decline use of contraception during the study period

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John M Timmerman, MD

Role: PRINCIPAL_INVESTIGATOR

UCLA / Jonsson Comprehensive Cancer Center

Locations

UC Davis Comprehensive Cancer Center

Davis, California, United States

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Countries

United States

Other Identifiers

NCI-2019-02887

Identifier Type: REGISTRY

Identifier Source: secondary_id

19-000604

Identifier Type: OTHER

Identifier Source: secondary_id

19-000604

Identifier Type: -

Identifier Source: org_study_id