Anakinra for Leukemia

(PACER Trial)

Overseen By Kevin O McNerney, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago

Must be taking: Anakinra

Disqualifiers: Pregnancy, Inadequate organ function, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 7 days post-CAR T infusion

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

How does the drug Anakinra differ from other treatments for leukemia?

Anakinra is unique because it is an interleukin-1 receptor antagonist, which means it blocks the action of a specific protein involved in inflammation, unlike traditional chemotherapy that targets rapidly dividing cells. This mechanism is different from the chemoradiation strategies currently used for aggressive natural killer cell leukemia, which focus on reducing toxicity while achieving a response. ^{1 2 3 4 5}

What is the purpose of this trial?

Objectives: The primary objective of this study will be to evaluate the impact of pre-emptive use of anakinra on the rate of severe cytokine release syndrome (CRS) following CD19-directed chimeric antigen receptor (CAR) T-cell therapy for B-acute lymphoblastic leukemia (B-ALL) in children and young adults. Patient Population: Children and young adults \<25 years of age undergoing CAR T-cell therapy for B-ALL with bone marrow disease burden of ≥5% involvement or detectable peripheral blasts within 2 weeks of the initiation of lymphodepleting chemotherapy. Study Design: This is a pilot single arm study. The investigators will inquire into the efficacy and safety of using anakinra pre-emptively to reduce the rate of severe CRS in patients with \>/=5% bone marrow blasts or lymphoblasts in the peripheral blood. Treatment Plan: This is a single arm unblinded study in which patients will receive anakinra, 2.5 mg/kg (max 100mg), IV every 12 hours starting at the onset of persistent fever (fever \>38.5⁰ C x 2 occurrences separated by at least 4 hours in a 24 hour period). If there is persistence or progression of CRS, anakinra frequency will be increased to 2.5mg/kg IV (max 100mg), every 6 hours. Anakinra will be continued until 48 hours after resolution of CRS and ICANS, and at least 7 days post-CAR T infusion. If dose and frequency of anakinra is increased, the increased dose of anakinra will be continued until 48 hours after resolution of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) and at least 7 days post-CAR T infusion. For CRS worsening beyond dose escalation of anakinra, CRS will be managed as per standard of care management. Participants will be followed for 12 months following enrollment in the study and disease evaluations will be performed as per routine clinical care following CAR T-cell therapy.

Eligibility Criteria

This trial is for children and young adults under 25 with B-acute lymphoblastic leukemia (B-ALL) who are undergoing CAR T-cell therapy. They must have a significant presence of cancer cells in their bone marrow or detectable cancer cells in the blood recently.

Inclusion Criteria

My leukemia has returned or didn't respond to treatment.

I (or my guardian) can understand and am willing to sign the consent form.

I am between 1 and 26 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anakinra pre-emptively to reduce the rate of severe CRS following CAR T-cell therapy

7 days post-CAR T infusion

Daily monitoring during hospitalization and clinical visits within the first 30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CRS and ICANS severity, infection rates, and survival

12 months

Treatment Details

Interventions

• Anakinra

Trial Overview The study tests if giving Anakinra before symptoms start can prevent severe cytokine release syndrome after CAR T-cell therapy in patients with high levels of leukemia cells. It's a pilot study where all participants receive Anakinra when they develop a persistent fever.

Participant Groups

Group I: Treatment Arm Experimental Treatment 1 Intervention

Anakinra is already approved in European Union, United States for the following indications:

Approved in European Union as Kineret for:

• Rheumatoid arthritis
• Cryopyrin-associated periodic syndromes
• Deficiency of interleukin-1 receptor antagonist
• COVID-19

Approved in United States as Kineret for:

• Rheumatoid arthritis
• Deficiency of interleukin-1 receptor antagonist
• Neonatal-onset multisystem inflammatory disease (NOMID)
• COVID-19

Who Is Running the Clinical Trial?

Ann & Robert H Lurie Children's Hospital of Chicago

Lead Sponsor

Trials

275

Recruited

5,182,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Aggressive Natural Killer Cell Leukemia: A Brief Overview of Its Genomic Landscape, Histological Features, and Current Management. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Differential expression levels of killer immunoglobin-like receptor genotype in patients with hematological malignancies between high-risk and standard-risk groups]. [2016]

3. China pubmed.ncbi.nlm.nih.gov

[Clinical and Pathological Characteristics of Aggressive Natural Killer Cell Leukemia Patients]. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Human interferon-alpha increases the cytotoxic effect of CD56(+) cord blood-derived cytokine-induced killer cells on human B-acute lymphoblastic leukemia cell lines. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission. [2022]