RecruitingPhase 1

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

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)

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
17 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests 19-28z/IL-18, a CAR T-cell therapy, for people with acute lymphoblastic leukemia (ALL) that came back or did not respond to treatment. T cells, a type of white blood cell, are collected from each person and changed in a lab to make the treatment. This takes about 2–4 weeks.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have B-cell ALL that came back or did not respond to treatment. People without the Philadelphia chromosome change must have had at least one multi-drug chemotherapy plan with both starting and follow-up treatment.
  • People with the Philadelphia chromosome change must have leukemia that stayed or grew after at least one newer targeted drug called a second- or third-generation tyrosine kinase inhibitor.
  • The first 3 patients must be at least 17. If a side effect that limits treatment occurs, the next 3 must also be at least 17. Later patients may be 12 or older.
  • Sign a consent form before any study procedures.
  • Past CD19-targeted treatment, including CAR T-cell therapy, is allowed if the latest bone marrow, blood, or tumor test shows the leukemia cells still have the CD19 marker.
  • A past donor stem cell transplant is allowed if it was at least 3 months before joining, with no graft-versus-host disease (donor cells attacking the body) in the past 4 weeks. Donor immune cell infusions must be at least 4 weeks before T-cell collection.
  • Past leukemia in the brain, spinal cord, or their lining is allowed if it is not the only disease site and there are no nervous system symptoms.
  • Meet the study's liver, kidney, lung, and heart test limits and its limits for daily activity. Children under 16 have a separate activity score requirement.

Who can't join

  • Have another active cancer, except certain skin cancers or a treated cancer with a low chance of returning. Burkitt leukemia or lymphoma and a certain advanced form of chronic myeloid leukemia (CML) are also excluded.
  • Have leukemia in the brain or spinal cord seen on scans, causing symptoms, or meeting the study's spinal fluid test limit. Successfully treated leukemia in these areas may be allowed.
  • Use certain medicines too close to T-cell collection or treatment: steroids above the allowed dose, chemotherapy, or hydroxyurea. Timing limits range from 72 hours to 1 week. Live, weakened vaccines within 4 weeks before collection are also excluded.
  • Have serious heart disease or certain heart procedures within the past 6 months.
  • Have a major immune or inflammatory illness affecting the brain or spinal cord, or severe autoimmune disease likely to need medicines that weaken the immune system. Treatment throughout the body for graft-versus-host disease within 4 weeks also excludes you.
  • Have HIV, active hepatitis B or C, or an uncontrolled infection, including COVID-19, when T cells are collected or given back.
  • Have other uncontrolled health or mental health conditions, or social or travel problems, that the study doctor believes would prevent following study requirements.
  • Are pregnant or breastfeeding.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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

Study sites (7)

NJ

NY