Study on Using Anakinra to Prevent Severe Reactions in Children and Young Adults Receiving CAR T-Cell Therapy for Leukemia

• Patient consent and parental assent will be obtained.

NOTE: Signed consent form must be obtained prior to any study procedures. Labs, marrows or other procedures obtained during routine clinical care maybe used for eligibility if obtained within the protocol required windows.

• Patients or their parents/legally authorized representatives (LARs) must have the ability to understand and the willingness to sign a written informed consent document.
• The effects of Anakinra on the developing human fetus are largely unknown. For this reason, patients of child-bearing potential (POCBP) and their partners with sperm-producing reproductive capacity must agree to use adequate contraception from time of informed consent, for the duration of study participation, and for 90 days following completion of Anakinra therapy. Should a POCBP become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must also agree to use adequate contraception with partners of childbearing potential from time of informed consent, for the duration of study participation, and 90 days after completion of administration.

Note: A POCBP is any patient (regardless of gender, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) with an egg-producing reproductive tract who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy

• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

• POCBP must have a negative serum or urine pregnancy test (women who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)

• Patients who are between the age of 1 to 26 years

• Relapsed or refractory B-acute lymphoblastic leukemia

  • 2nd or greater marrow relapse OR

  • Central nervous system (CNS) relapse OR

  • Any relapse after allogeneic hematopoietic stem cell transplant (HSCT) OR

  • Refractory disease defined by not achieving an minimal residual disease (MRD)-negative complete remission (CR) after ≥ 2 chemotherapy cycles (1 cycle for relapsed patients) OR

  • Ineligible for allogeneic HSCT because of:

    • Comorbid disease
    • Other contraindications to allogeneic HSCT conditioning
    • No suitable donor
    • Prior HSCT
    • Declines HSCT as the therapeutic option after documented discussion, with expected outcomes, about the role of HSCT with a HSCT physician

  • Documentation of CD19+ tumor expression in the bone marrow, peripheral blood, cerebrospinal fluid (CSF), or tumor tissue by flow cytometry at relapse, or a recent sample in the case of refractory disease. If the patient has received CD19-directed Pre-emptive anakinra for severe CRS prevention therapy, the flow cytometry should be obtained after this therapy to show CD19 expression.

• Adequate organ function defined as:

  • Alanine aminotransferase (ALT) < 500 U/L
  • Bilirubin ≤2.0 mg/dL
  • Minimum pulmonary reserve defined as ≤Grade 1 dyspnea, pulse oximetry >92% on room air; diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% (corrected for anemia) if pulmonary function tests (PFTs) are clinically appropriate as determined by the treating investigator.
  • Left ventricular shortening fraction ≥ 28% or ejection fraction ≥40% confirmed by echocardiography (ECHO), or adequate ventricular function documented by imaging or a cardiologist.
  • Serum creatinine below the values in the below table, based on age/sex assigned at birth: Maximum Serum Creatinine (mg/dL) Age (years) Male Female 1 to <2 0.6 0.6 2 to <6 0.8 0.8 6 to <10 1.0 1.0 10 to <13 1.2 1.2 13 to <16 1.5 1.4 ≥16 1.7 1.4

• Bone marrow disease burden of ≥5% or peripheral blasts within 2 weeks of the start of lymphodepleting chemotherapy

• Receiving commercially available tisagenlecleucel