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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Enrolling; Phase 1

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

Treatments: Biological: 19-28z/IL-18 CAR T cells

Study type: Interventional

Funder types: Other

Identifiers

NCT06287528

23-307

Details and patient eligibility

About

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.

Enrollment: 18 estimated patients

Sex: All

Ages: 17+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

Dose Level 1

Experimental group

Description:

0.5x106 CAR-T cell/kg without lymphodepleting chemotherapy (LDC)

Treatment:

Biological: 19-28z/IL-18 CAR T cells

Dose Level 2

Experimental group

Description:

0.5x106 cells/kg with lymphodepleting chemotherapy (LDC)

Treatment:

Biological: 19-28z/IL-18 CAR T cells

Dose Level 3

Experimental group

Description:

1x106 cells/kg with lymphodepleting chemotherapy (LDC)

Treatment:

Biological: 19-28z/IL-18 CAR T cells