Philadelphia-Negative ALL, Philadelphia-Positive ALL, Refractory Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia (ALL), Refractory Acute Lymphoid Leukemia in Relapse, Relapsed ALL, Adult
Conditions
Keywords
Philadelphia-Negative ALL, Philadelphia-Positive ALL, Philadelphia chromosome negative (Ph-negative) B-ALL, Philadelphia chromosome positive (Ph+ positive) B-ALL, Relapsed ALL, Adult, Refractory Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia (ALL), Refractory Acute Lymphoid Leukemia in Relapse, 19-28z/IL-18, 23-307, Memorial Sloan Kettering Cancer Center
Brief summary
Participants will have a sample of their white blood cells, called T cells, collected using a procedure called leukapheresis. The collected T cells will be sent to a laboratory to be changed (modified) to become 19-28z/IL-18, the CAR T-cell therapy that participants will receive during the study. Making the participants' study therapy will take about 2-4 weeks.
Interventions
BIOLOGICAL19-28z/IL-18 CAR T cells
19-28z/IL-18 CAR T cells are an investigational new drug (IND) for the treatment of R/R B-ALL
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity as determined by CTCAE, version 5.0 | 4 weeks | The primary objective is to determine the safety of 19-28z/IL18 CAR T cells in patients with R/R ALL. Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. |
Countries
United States
Contacts
CONTACTJae Park, MD
CONTACTMark Geyer, MD
PRINCIPAL_INVESTIGATORJae Park, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed