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

Официальное название

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)

Обзор

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.

Вмешательства

• Биопрепарат 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

Первичные конечные точки

• Toxicity as determined by CTCAE, version 5.0 [Срок оценки: 4 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 7 центров

• Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities) — Basking Ridge
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale
• Memorial Sloan Kettering Cancer Suffolk-Commack (Limited Protocol Activities) — Commack
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale

Идентификаторы

NCT: NCT06287528 · 23-307

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗