Clinical trial NCT04359784: Anakinra for the Prevention of Cytokine Release Syndrome and Neurotoxicity in Patients With B-Cell Non-Hodgkin Lymphoma Receiving CD19-Targeted CAR-T Cell Therapy
Official title: Phase 2 Pilot Study to Evaluate Efficacy and Safety of Anakinra to Prevent CD19-Targeted CAR-T Cell-Related Cytokine Release Syndrome (CRS) and Neurotoxicity in Patients With B Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-Cell Non-Hodgkin Lymphoma
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: Swedish Orphan Biovitrum
First posted: 2020-04-24
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This phase II trial studies how well anakinra works in decreasing the occurrence of cytokine release syndrome (CRS) and damage to the nerves (neurotoxicity) in patients with B-cell non-Hodgkin lymphoma who are receiving CD-19 targeted chimeric antigen receptor T-cell (CAR-T) therapy. CAR-T cell therapy may be complicated by two potentially life-threatening side effects: CRS and neurotoxicity. Anakinra is a drug typically used to treat rheumatoid arthritis, but may also help in preventing CAR-T cell-related cytokine release syndrome and neurotoxicity.

Detailed description: OUTLINE:

Patients receive anakinra intravenously (IV) \[previously subcutaneously (SC) for some patients\] over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, positron emission tomography/computed tomography (PET/CT) or CT, bone marrow aspirate (BMA) and biopsy (if clinically indicated), and lumbar puncture (if clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.

After completion of lisocabtagene maraleucel infusion, patients are followed up periodically for up to 90 days.

Eligibility criteria: Inclusion Criteria:

* Subjects must be 18 years of age or older
* Karnofsky performance status of \>= 60%
* Patients with B-cell non-Hodgkin lymphoma (B-NHL) and eligible for treatment with liso-cel. Patients treated with non-conforming (out-of-specification) liso-cell may remain on study.
* Negative serum pregnancy test within 2 weeks of enrollment for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
* Fertile male and female subjects must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last dose of anakinra
* Ability to understand and provide informed consent

Exclusion Criteria:

* Subjects requiring ongoing daily corticosteroid therapy at a dose of \> 15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable
* Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the principal investigator (PI)
* Known hypersensitivity to Escherichia € coli-derived proteins, anakinra, or to any component of the product
* Major organ dysfunction defined as:

  * Serum creatinine \> 2.5 mg/dL
  * Significant hepatic dysfunction (Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 5x upper limit of normal; bilirubin \> 3.0 mg/dL) unless due to malignancy or Gilbert's syndrome in the opinion of the PI or designee
  * Subjects with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing. Those with a forced expiratory volume in 1 second (FEV1) of \< 50% of predicted or diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) \< 40% will be excluded
  * Significant cardiovascular abnormalities as defined by any one of the following: New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of \< 35%
* Uncontrolled serious and active infection

Primary outcomes:
measure: Absence of any grade cytokine release syndrome (CRS)
timeFrame: Up to 28 days after lisocabtagene maraleucel (liso-cel) infusion
Secondary outcomes:
measure: CRS grade
timeFrame: Up to 28 days after liso-cel infusion
measure: Neurotoxicity grade
timeFrame: Up to 28 days after liso-cel infusion
measure: Rate of hospitalization after liso-cel treatment
timeFrame: Up to 28 days after liso-cel infusion
measure: Duration of hospitalization after liso-cel treatment
timeFrame: Up to 28 days after liso-cel infusion
measure: Corticosteroid usage after liso-cel treatment
timeFrame: Up to 28 days after liso-cel infusion
measure: Disease response to liso-cel
timeFrame: Approximately at 28 and 90 days after liso-cel infusion
measure: Adverse events (AEs)
timeFrame: Up to 28 days after liso-cel infusion
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Jordan Gauthier
role: PRINCIPAL_INVESTIGATOR
References: