a study of 19-28z/il-18 in people with acute lymphoblastic leukemia (all)

Conditions: Philadelphia-Negative ALL; Philadelphia-Positive ALL; Relapsed ALL, Adult; Refractory Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoid Leukemia in Relapse

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.


Eligibility criteria:
inclusion criteria: * patients must have r/r all meeting one of the following criteria: * for philadelphia chromosome negative (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 positive (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 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: should be stopped one week prior to leukapheresis or starting 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. for those patients who have had a recent covid-19 infection, at least 4 weeks should be passed before the covid-19 infection date and 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

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