A Study of 19-28z/IL-18 in People With Acute Lymphoblastic Leukemia (ALL)

Refractory Acute Lymphoblastic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06287528
• Other study ID #: 23-307
• Status: Recruiting
• Phase: Phase 1
• Start date: February 23, 2024
• Est. completion date: February 23, 2028

Study information

• Verified date: April 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Jae Park, MD
• Phone: 646-608-3743
• Email: parkj6[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: February 23, 2028
• Est. primary completion date: February 23, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Philadelphia-Negative ALL
• Philadelphia-Positive ALL
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrence
• Refractory Acute Lymphoblastic Leukemia
• Refractory Acute Lymphoblastic Leukemia (ALL)

Intervention

Biological:
• 19-28z/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

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Suffolk-Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity as determined by CTCAE, version 5.0	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.	4 weeks

External Links

•   Memorial Sloan Kettering Cancer Center