Treatment for relapsed or refractory CD19-positive leukemia using allogeneic memory T-cells

A Phase I Study Evaluating Allogeneic Memory T Cells Engineered to Express Chimeric Antigen Receptors Specific for CD19 for the Treatment of Pediatric and Young Adult Patients ≤ 21 Years of Age With Relapsed or Refractory CD19-Positive Leukemia

This study is testing a new CAR T-cell therapy using special immune cells to see if it can help young people with tough-to-treat leukemia feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: N/A to 21 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (Academic / other)
• Drugs / interventions: CAR T, chemotherapy
• Locations: 1 site (Memphis, Tennessee)
• Trial ID: NCT04881240 on ClinicalTrials.gov

What this trial studies

This Phase I clinical study evaluates the safety and maximum tolerated dose of a novel CAR T-cell therapy using allogeneic memory T-cells that target CD19 for patients aged 21 and under with relapsed or refractory CD19-positive leukemia. The study employs a dose escalation design to assess the treatment's safety profile and potential anti-leukemic activity. Participants will be divided into two groups based on their prior stem cell transplant status, with a total of up to 60 participants expected. The study also aims to monitor the incidence of graft-versus-host disease following treatment.

Who should consider this trial

Good fit: Ideal candidates are pediatric patients aged 21 or younger with relapsed or refractory CD19-positive leukemia.

Not a fit: Patients who have not been diagnosed with CD19-positive leukemia or those who are not suitable for CAR T-cell therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for young patients with difficult-to-treat leukemia.

How similar studies have performed: Other studies using CAR T-cell therapies have shown promising results, indicating potential success for this novel approach.

Eligibility criteria

Inclusion Criteria Eligibility Criteria for Donors: Apheresis and Manufacturing

* Age ≥ 18 years old
* At least single haplotype matched (≥ 3/6) family member
* HIV negative
* For females of child bearing age: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment AND Not lactating with intent to breastfeed
* Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance

For Cohort A only, identified recipient with relapsed and/or refractory CD19-positive leukemia

For Cohort B only, iIdentified recipient with relapsed and/or refractory CD19-positive leukemia who is not suitable to receive autologous CD19-CAR T-cell therapy as defined by the following:

* Relapsed and/or refractory disease despite prior treatment with autologous CD19- CAR T-cell therapy
* History of prior autologous leukapheresis failure
* History of prior autologous CAR T-cell manufacturing failure
* Unable to undergo autologous leukapheresis in the opinion of the study PI(s): examples may include - patient small size/low weight, inadequate T-cell counts, rapidly progressive leukemia, clinical status not amenable to apheresis

Eligibility Criteria for Patients: Treatment

* Age ≤ 21 years old
* Relapsed and/or refractory CD19-positive leukemia\*:

  * Refractory disease (defined as any of the following):

    * Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission
    * Refractory disease despite salvage therapy
  * Relapsed disease (defined as any of the following):

    * 2nd or greater relapse
    * Any relapse after allogeneic hematopoietic cell transplantation (HCT)
    * 1st relapse if patient requires an allogeneic HCT as part of standard of care relapse therapy, but is found to be ineligible and/or unsuitable for HCT

CD19-positivity confirmed within 2 months and after receipt of any CD19-directed therapy

* Patient cohorts:

  * Cohort A: patient has previously received a HCT from the selected CAR T-cell donor
  * Cohort B - patient has NOT previously received a HCT from the selected CAR T-cell donor.
* For Cohort B only, not suitable to receive autologous CD19-CAR T-cell therapy as defined above in Criteria: Eligibility Criteria for Donors: Apheresis and Manufacturing
* Detectable medullary CD19-positive leukemia
* Estimated life expectancy of ≥ 8 weeks
* Karnofsky or Lansky performance score ≥ 50
* No CNS-3 disease or any level of detectable leukemia in CNS with associated neurologic symptoms
* If history of allogeneic HCT (regardless of donor type), prior to planned CAR T-cell infusion, must meet the following criteria:

  * ≥ 3 months from HCT
  * have recovered from prior HCT therapy
  * have no evidence of active GVHD within prior 2 months
  * have not received a donor lymphocyte infusion (DLI) within the 28 days prior to planned CAR T-cell infusion
* Adequate cardiac function: left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25% (function may be supported by pharmacologic therapy)
* EKG without evidence of clinically significant arrhythmia
* Adequate renal function: creatinine clearance or radioisotope GFR 50 ml/min/1.73m2 (GFR 40 ml/min/1.73m2 if \< 2 years of age)
* Adequate pulmonary function: forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing
* Total bilirubin ≤ 3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age
* No history of HIV infection
* No evidence of severe, uncontrolled bacterial, viral or fungal infection
* Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy
* For females of child bearing age:

  * Not pregnant with negative serum or urine pregnancy test ≤ 7 days prior to enrollment AND Not lactating with intent to breastfeed
* If sexually active, agreement to use birth control until 6 months after CAR T-cell infusion
* No history of hypersensitivity reactions to murine protein-containing products
* Not receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone ≤ 7 days prior to CAR T-cell infusion
* Not receiving systemic therapy ≤ 14 days prior to CAR T-cell infusion, which will interfere with the activity of the CAR T-cell product in vivo (in the opinion of the study PI(s))
* Not receiving intrathecal chemotherapy ≤ 7 days prior to CAR T-cell infusion

Exclusion Criteria:

NA

Where this trial is running

Memphis, Tennessee

• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Aimee C. Talleur, MD — St. Jude Children's Research Hospital
• Study coordinator: Aimee C. Talleur, MD

Conditions Acute Lymphoblastic Leukemia, in Relapse; Acute Lymphoblastic Leukemia, Refractory; Pediatric ALL