RECRUITING

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 Philadelphia chromosome negative (Ph-negative) B-ALL Philadelphia chromosome positive (Ph+ positive) B-ALL 19-28z/IL-18 23-307 Memorial Sloan Kettering Cancer Center

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2024-02-23

Study Completion:2028-02-23

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06287528

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:17 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Jae Park, MD

CONTACT

646-608-3743

parkj6@mskcc.org

Mark Geyer, MD

CONTACT

646-608-3745

geyerm@mskcc.org

Principal Investigator

Jae Park, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Cancer Suffolk-Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Jae Park, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-02-23

Study Completion Date2028-02-23

Study Record Updates

Study Start Date2024-02-23

Study Completion Date2028-02-23

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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