A Phase 2 Trial of Anakinra for the Prevention of CAR-T Cell Mediated Neurotoxicity

NCT04150913 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-348
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying the combination of anakinra and axicabtagene ciloleucel to reduce the occurrence of the side effects Cytokine Release Syndrome (CRS) and neurologic toxicities with relapsed or refractory Non-Hodgkin lymphoma (NHL).

• Relapsed NHL is the condition of returned Non-Hodgkin lymphoma.
• Refractory NHL is the condition of previous treatment resistant Non-Hodgkin lymphoma.
• Cytokine Release Syndrome (CRS) is a group of side effect symptoms that can include nausea, headache, rapid heartbeat, shortness of breath, kidney damage, and rash.
• Neurologic toxicity is nervous system disorder characterized by confusion This research study involves two drugs:
• Anakinra
• Axicabtagene Ciloleucel.

Conditions

Non Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Relapsed Non Hodgkin Lymphoma; Neurotoxicity; Neurotoxicity Syndromes; Cytokine Release Syndrome

Keywords

Non Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Relapsed Non Hodgkin Lymphoma; Neurotoxicity; Neurotoxicity Syndromes; Cytokine Release Syndrome

Outcome Measures

Primary Outcomes (1)

• Rate of Neurotoxicity as Per CTCAE v4.03 Criteria

  The incidence of grade 2+ neurotoxicity is reported below and was assessed using CTCAE (Common Terminology Criteria for Adverse Events) v4.04 criteria. Neurotoxicity is a serious side effect of cancer treatments that can impact the central and peripheral nervous systems. Neurotoxicity manifestations vary and can include confusion, obtundation, seizures, hallucinations, aphasia, ataxia, and more rarely, profound cerebral edema.

  30 Days

Secondary Outcomes (6)

• Objective Response Rate

  24 Months

• Duration of Response

  first objective response to disease progression death regardless of cause up 24 Months

• Progression-free Survival

  infusion date to the date of disease progression or death from any cause up 24 Months

• Overall Survival

  time from axicabtagene ciloleucel infusion to the date of death or analysis data cutoff date will be censored at last contact date up to 24 months.

• Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher

  24 Months

Study Arms (1)

Anakinra and Axicabtagene Ciloleucel

EXPERIMENTAL

Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. * Screening * Enrollment/Leukapheresis period * Bridging therapy (if applicable) * Lymphodepleting chemotherapy period * Investigational Product (IP) treatment period * Anakinra * Axicabtagene Ciloleucel * Post treatment assessment period * Long term follow-up period

Drug: Anakinra; Drug: Axicabtagene Ciloleucel

Interventions

Anakinra DRUG

Subcutaneous, dosage per protocol. Day 0 through Day 6.

Also known as: Kineret®

Anakinra and Axicabtagene Ciloleucel

Axicabtagene Ciloleucel DRUG

Once, intravenous infusion, dosage per protocol

Anakinra and Axicabtagene Ciloleucel

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including 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.
• At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma 1. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy however steroids only require a 7-day washout. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc).
• Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia)
• Age 18 or older
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• ANC ≥1000/uL
• Platelet count ≥75,000/uL
• Absolute lymphocyte count ≥100/uL
• Adequate renal, hepatic, pulmonary and cardiac function defined as:
• Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
• Serum ALT/AST ≤2.5 ULN
• Total bilirubin ≤1.5 mg/dl, except in subjects with Gilbert's syndrome.
• Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion, and no clinically significant ECG findings
• No clinically significant pleural effusion

You may not qualify if:

• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
• History of Richter's transformation of CLL
• Autologous stem cell transplant within 6 weeks of planned axicabtagene ciloleucel infusion
• History of allogeneic stem cell transplantation
• Prior CD19 targeted therapy with the exception of subjects who received axicabtagene ciloleucel in this study and are eligible for re-treatment
• Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
• History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
• History of HIV infection or acute or chronic active hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines.
• Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted
• Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
• History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
• Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
• Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome)

Sponsors & Collaborators

• Marcela V. Maus, M.D.,Ph.D.: lead
• Kite, A Gilead Company: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Frigault MJ, Yao N, Berger TR, Wehrli M, Gallagher KME, Horick N, Graham CE, Jacobson CA, Chen YB, Leick MB, DeFilipp Z, El-Jawahri AR, Johnson PC, Dolaher M, Katsis K, Kim AI, Crombie J, Merryman RW, Cook D, Trailor M, Cho H, Jeffrey R 3rd, Shen R, Filosto S, Nater J, Getz G, Haradhvala NJ, Maus MV. Single-cell dynamics of breakthrough toxicities after anakinra prophylaxis for axicabtagene ciloleucel in lymphoma. Blood Adv. 2025 May 13;9(9):2122-2135. doi: 10.1182/bloodadvances.2024015161.

  PMID: 39928957 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Neurotoxicity Syndromes; Cytokine Release Syndrome

Interventions

Interleukin 1 Receptor Antagonist Protein; axicabtagene ciloleucel

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Limited number of patients enrolled into the study

Results Point of Contact

• Title: Director, Cellular Immunotherapy Program
• Organization: Massachusetts General Hospital

mghcancercenter@partners.org

857-367-1486

Study Officials

• Matt J Frigault, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 5, 2019
• Study Start: October 1, 2020
• Primary Completion: October 30, 2023
• Study Completion: October 31, 2024
• Last Updated: November 25, 2025
• Results First Posted: May 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)