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Non Hodgkin LymphomaPhase 2NCT04150913

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

A Phase 2 study testing Anakinra and Axicabtagene Ciloleucel in people with Non Hodgkin Lymphoma and Refractory Non-Hodgkin Lymphoma, run by Marcela V. Maus, M.D.,Ph.D. at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anakinra and Axicabtagene Ciloleucel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesUnited States
Study dates
1 Oct 2020to 31 Oct 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

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
Read more

This research study involves two drugs:

  • Anakinra
  • Axicabtagene Ciloleucel.
Read the detailed description

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 are anticipated to 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).
Being tested
Anakinra, Axicabtagene Ciloleucel
Keywords
Non Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, Relapsed Non Hodgkin Lymphoma, Neurotoxicity, Neurotoxicity Syndromes, Cytokine Release Syndrome
Medical subject headings
Lymphoma, Non-Hodgkin, Neurotoxicity Syndromes, Cytokine Release Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AnakinraDrug

    Also called Kineret®

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

  • Axicabtagene CiloleucelDrug

    Once, intravenous infusion, dosage per protocol

Study groups in NCT04150913
Study groupRoleWhat they receive
Anakinra and Axicabtagene CiloleucelExperimentalPatients 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
Receives: Drug: Anakinra; Drug: Axicabtagene Ciloleucel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 30 Days

Secondary outcomes (6)

  1. Objective Response Rate

    Objective response rate (ORR) is defined as the incidence of either a complete response (CR) or a partial response (PR) by the revised IWG Response Criteria for Malignant Lymphoma. All participants who don't meet the ORR criteria by the analysis data cutoff date will be considered non-responders.

    • CR = complete disappearance of all detectable clinical evidence of disease and disease related symptoms if present before therapy; PET scan negative; lymph nodes/nodal masses regressed to normal size; normal size spleen/liver on CT scan; bone marrow aspirate and biopsy shows no evidence of disease by morphology or negative by IHC.
    • PR = ≥ 50% decrease in sum of the product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses; no size increase of nodes/liver/spleen; no new sites of disease; post-treatment PET scan positive in ≥ 1 previously involved site.

    Measured: 24 Months

  2. Duration of Response

    Among participants who experience an objective response, duration of response (DOR) is defined as the date of their first objective response to disease progression per the revised IWG Response Criteria for Malignant Lymphoma, or death regardless of cause. Participants not meeting the criteria for progressive disease (PD) or death by the analysis data cutoff date will be censored at their last evaluable disease assessment date and their response will be noted as ongoing.

    • PD = ≥ 50% increase from nadir in the sum of the products of at least two lymph nodes; ≥ 50% increase in product of the diameters of single node; new lesion >1.5 cm; ≥ 50% size increase of splenic/hepatic nodules; ≥ 50% increase in longest diameter of any single previously identified node more than 1 cm in its short axis; PET scan positive

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

  3. Progression-free Survival

    Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for progression-free survival time

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

  4. Overall Survival

    Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for OS.

    Measured: 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.

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

    Subject incidence rates of adverse events including all, serious, fatal, CTCAE version 4.03 Grade 3 or higher and treatment related AEs reported throughout the conduct of the study will be tabulated by preferred term and system organ class

    Measured: 24 Months

  6. Rate of Cytokine Release Syndrome (CRS) as Per Lee 2014 for CRS

    The incidence of max grade 2+ CRS will be assessed

    Measured: Within 30 days after infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2019
  2. Study start1 Oct 2020
  3. Primary completion30 Oct 2023
  4. Study completion31 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04150913
Sponsor's protocol ID
19-348
Status last verified
Nov 2025
First submitted
1 Nov 2019
Last updated
25 Nov 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Publications

  • 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.

    PubMed 39928957

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anakinra and Axicabtagene Ciloleucel in people with Non Hodgkin Lymphoma and Refractory Non-Hodgkin Lymphoma, run by Marcela V. Maus, M.D.,Ph.D. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Neurotoxicity as Per CTCAE v4.03 Criteria (time frame: 30 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04150913, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2025.

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