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

  • End date
    Nov 10, 2024
  • participants needed
  • sponsor
    Marcela V. Maus, M.D.,Ph.D.
Updated on 10 November 2021
platelet count
hodgkin's disease
absolute neutrophil count
ejection fraction
measurable disease
pleural effusion
gilbert's syndrome
follicular lymphoma
diffuse large b-cell lymphoma
b-cell lymphoma
large b-cell lymphoma
refractory non-hodgkin's lymphoma
nervous system disorder
non-hodgkin's lymphoma refractory


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.


This Phase 2, single center, open-label 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 in people with relapsed or refractory Non-Hodgkin lymphoma (NHL).

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

  • This research study involves two drugs:
  • Anakinra
  • Axicabtagene Ciloleucel
  • A total of 20 participants will be enrolled to this trial
  • The U.S. Food and Drug Administration (FDA) has not approved anakinra for use in treatment of Non-Hodgkin lymphoma (NHL).

Condition Sun Poisoning, Lymphoma, Refractory Non Hodgkin Lymphoma, nervous system disorder, non-hodgkin's lymphoma (nhl), Toxic encephalopathy, Non-Hodgkin's Lymphoma, neurotoxicity, Cytokine Release Syndrome, neurotoxic effect, Relapsed Non Hodgkin Lymphoma, Neurologic Disorders, Poisoning
Treatment Anakinra, Axicabtagene Ciloleucel
Clinical Study IdentifierNCT04150913
SponsorMarcela V. Maus, M.D.,Ph.D.
Last Modified on10 November 2021


Yes No Not Sure

Inclusion Criteria

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
Baseline oxygen saturation >92% on room air
Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential) Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

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)
Primary immunodeficiency
History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
History of severe immediate hypersensitivity reaction to any of the agents used in this study
Live vaccine 6 weeks prior to planned start of conditioning regimen
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential
Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of axicabtagene ciloleucel
In the investigators judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
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