Treatment for Acute Lymphoblastic Leukemia using modified T cells
A Phase I Trial of CD19-targeted Chimeric Antigen Receptor (CAR) T Cells That Constitutively Secrete Interleukin 18 (19-28z/IL-18) in Patients With Relapsed or Refractory (R/R) Acute Lymphoblastic Leukemia (ALL)
This study is testing a new treatment using specially modified T cells to see if it can help people with Acute Lymphoblastic Leukemia who haven't had success with other therapies.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 18 (estimated) |
| Ages | 17 Years and up |
| Sex | All |
| Sponsor | Memorial Sloan Kettering Cancer Center Academic / other |
| Drugs / interventions | CAR-T, CAR T, chemotherapy, prednisone |
| Locations | 7 sites (Basking Ridge, New Jersey and 6 other locations) |
| Trial ID | NCT06287528 on ClinicalTrials.gov |
What this trial studies
This study involves collecting a patient's T cells through a procedure called leukapheresis, which are then modified in a laboratory to create a specific CAR T-cell therapy known as 19-28z/IL-18. The modified T cells will be administered to patients with various forms of Acute Lymphoblastic Leukemia (ALL), including both Philadelphia-negative and Philadelphia-positive types, who have not responded to previous treatments. The process of modifying the T cells is expected to take about 2-4 weeks before treatment can begin. This is a Phase 1 interventional study aimed at assessing the safety and efficacy of this novel therapy.
Who should consider this trial
Good fit: Ideal candidates for this study are patients aged 12 years and older with relapsed or refractory Acute Lymphoblastic Leukemia who have not responded to prior treatments.
Not a fit: Patients with early-stage ALL or those who have not undergone prior treatment may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with refractory or relapsed Acute Lymphoblastic Leukemia.
How similar studies have performed: Other studies using CAR T-cell therapies have shown promising results in treating various types of leukemia, indicating potential success for this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Patients must have R/R ALL meeting one of the following criteria: * For Philadelphia chromosome (Ph) negative B-ALL: Refractory or relapsed disease to at least 1 prior multiagent systemic chemotherapy regimen that included both induction and consolidation therapy * For Philadelphia chromosome (Ph) positive B-ALL: patients must have exhibited persistent or progressive disease following at least 1 prior second- or third-generation tyrosine kinase inhibitor * Signed informed consent form (ICF) prior to any study procedures * Age: The first 3 patients enrolled into the study will be ≥ 17 years of age at time of enrollment. If a DLT is observed, the additional 3 patients in this cohort will also be ≥ 17 years of age. Additional patients will be ≥12 years of age at time of enrollment. * Documentation of CD19 positivity on leukemia blasts if prior anti-CD19 treatment * History of prior allogeneic hematopoietic stem cell transplant (HSCT) is allowed if ≥3 months from time of enrollment and no evidence of acute or chronic graft versus host disease (GVHD) within 4 weeks prior to enrollment * Donor lymphocyte infusions (DLI) permitted if ≥4 weeks prior to leukapheresis * History of secondary CNS or meningeal involvement allowed if: * cannot be the only site of disease * absence of neurologic symptoms, such as: seizures, stroke-like deficits, altered mental status, aphasia, or psychosis * Adequate organ function at time of screening, including: * ALT or AST ≤5x ULN and total bilirubin ≤2 (or ≤3 if history of Gilbert's syndrome or leukemic infiltration of the liver) * Serum creatinine \<2.0mg/100mL * SaO2 ≥92% on room air * Left ventricular ejection fraction (LVEF) ≥50% within 1 month of screening * ECOG performance status 0-1 or Lansky performance status ≥ 60 for patients \< 16 years old * Prior CD19-targeted therapies (including CD19 CAR-T cell and CD19 bispecific T-cell engagers) are allowed including anti-CD19 CAR T therapy, as long as CD19 positivity is confirmed on most recent bone marrow, blood or tumor biopsy Exclusion Criteria: * Concurrent active malignancy excluding: nonmelanoma skin cancer or localized solid tumor that has undergone definitive therapy and with low risk of recurrence, e.g., prostate, breast * Burkitt's leukemia or lymphoma or CML in lymphoid blast crisis * Radiologically detected or symptomatic CNS disease or CNS 3 disease (i.e., presence of ≥5/µL WBCs in CSF). Subjects with adequately treated CNS leukemia are eligible. * The following medications are excluded: * Steroids: Therapeutic doses of corticosteroids (greater than 10mg daily of prednisone or its equivalent) within 7 days of leukapheresis or 72 hours prior to CAR T cell infusion. * Chemotherapy: Systemic chemotherapy should be stopped one week prior to leukapheresis or starting CAR T cell infusion or lymphodepleting chemotherapy. Hydroxyurea for cytoreduction can be administered up to 72 hours before leukapheresis or CAR T cell infusion. * History of class III-IV New York Heart Association (NYHA) heart failure, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac condition within 6 months of screening * Patients with history of significant autoimmune disease and/or inflammatory condition affecting the CNS are ineligible * Systemic treatment for GVHD within 4 weeks prior to enrollment * Patients with known severe autoimmune disease (e.g., Crohn's, rheumatoid arthritis, or lupus) that in the investigator's opinion has high likelihood of requiring systemic immune suppressive medications * Patients with HIV infection * Patients with active hepatitis B infection (as manifested by either detectable hepatitis B virus DNA by PCR and/or positivity for hepatitis B surface antigen) * Patients with active hepatitis C infection (as manifested by detectable hepatitis C virus RNA by PCR) * Patients with uncontrolled systemic fungal, bacterial, viral or other infection including COVID-19 at time of leukapheresis or at time of CAR T cell infusion. * Other uncontrolled medical or psychological conditions as well as social or logistical issues that may interfere with compliance with the protocol, as determined by the investigator * Treatment with live, attenuated vaccine \<4 weeks prior to leukapheresis * Pregnant or lactating/breastfeeding women
Where this trial is running
Basking Ridge, New Jersey and 6 other locations
- Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Cancer Suffolk-Commack (Limited Protocol Activities) — Commack, New York, United States (Recruiting)
- Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (Recruiting)
- Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
- Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States (Recruiting)
Study contacts
- Principal investigator: Jae Park, MD — Memorial Sloan Kettering Cancer Center
- Study coordinator: Jae Park, MD
- Email: parkj6@mskcc.org
- Phone: 646-608-3743
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.