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

NCT04205838 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: 19-000604NCI-2019-02887
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (2)

• Number of patients who met the eligibility criteria to receive and did receive anakinra

  The study will be considered feasible if 8 study participants are enrolled over 12 months at University of California, Los Angeles.

  Up to 12 months

• Rate of severe chimeric antigen receptor T-cell-related encephalopathy syndrome (ICANS)

  Will be defined as grade \>= 3 neurotoxicity by Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03. The proportion of patients developing severe ICANS and the corresponding 90% binomial exact confidence interval (CI) will be reported.

  Up to 30 days

Secondary Outcomes (6)

• Objective response rate (ORR)

  Up to 90 days

• Proportion of patients who received anakinra and develop ICAN

  Up to 30 days

• Duration of neurotoxicity

  From first day of CRES of any grade to complete resolution of CRES, assessed up to 100 days

• Duration of neurotoxicity

  From first day of ICANS of >= grade 3 to improvement of ICANS to < grade 3, assessed up to 100 days

• Persistent hepatotoxicity

  Up to 100 days

Other Outcomes (9)

• ICANS grade

  up to 30 days

• Cytokine release syndrome (CRS) grade

  Up to 30 days

• Changes in inflammatory markers

  Baseline up to 6 days following initiation of anakinra

Study Arms (1)

Prevention (anakinra, CAR T-cell therapy)

EXPERIMENTAL

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.

Biological: Anakinra; Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Fludarabine Phosphate

Interventions

Anakinra BIOLOGICAL

Given SC

Also known as: Kinaret, Kineret, rIL-1ra, rIL1RN

Prevention (anakinra, CAR T-cell therapy)

Axicabtagene Ciloleucel BIOLOGICAL

Given via infusion

Also known as: KTE C19, KTE-C19, KTE-C19 CAR, Yescarta

Prevention (anakinra, CAR T-cell therapy)

Cyclophosphamide DRUG

Given via infusion

Also known as: (-)-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

Prevention (anakinra, CAR T-cell therapy)

Fludarabine DRUG

Given via infusion

Also known as: Fluradosa

Prevention (anakinra, CAR T-cell therapy)

Fludarabine Phosphate DRUG

Given via infusion

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Prevention (anakinra, CAR T-cell therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead

Study Sites (2)

UC Davis Comprehensive Cancer Center

Davis, California, 95817, United States

Location

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Disease Progression

Interventions

Interleukin 1 Receptor Antagonist Protein; Receptors, Interleukin-6; axicabtagene ciloleucel; Cyclophosphamide; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Receptors, Interleukin; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• John M Timmerman, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: December 20, 2019
• Study Start: March 4, 2020
• Primary Completion: February 19, 2026
• Study Completion: February 19, 2026
• Last Updated: February 27, 2026

Record last verified: 2025-07

Locations

US (2)