CAR T cell therapy for young patients with CD19-positive leukemia

CAR T CELL Therapy for Pediatric, Adolescent and Young Adult Patients With CD19-Positive Leukemia: An Investigation of Lymphodepleting Chemotherapy Pharmacokinetics

This study is testing a new treatment combining CAR T cell therapy and chemotherapy to see if it helps young patients with hard-to-treat leukemia.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: N/A to 21 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (other)
• Drugs / interventions: CAR T, chemotherapy, chimeric antigen receptor, cyclophosphamide, fludarabine
• Locations: 1 site (Memphis, Tennessee)
• Trial ID: NCT06847269 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of CAR T cell therapy combined with lymphodepleting chemotherapy in treating pediatric, adolescent, and young adult patients with refractory or relapsed CD19-positive leukemia. Participants will undergo a single course of chemotherapy using age-based doses of fludarabine and cyclophosphamide, followed by an infusion of modified T cells designed to target cancer cells. The study aims to assess the optimal dosing of chemotherapy, the persistence of CAR T cells in the body, and the overall effectiveness and safety of this treatment approach.

Who should consider this trial

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

Not a fit: Patients with CD19-negative leukemia or those who are not eligible for autologous apheresis 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, potentially improving survival rates.

How similar studies have performed: Previous studies using CAR T cell therapy for leukemia have shown promising results, indicating potential success for this approach.

Eligibility criteria

Autologous Apheresis and Manufacturing

Inclusion Criteria:

* CD19+ leukemia\*\* with any of the following:

  * Refractory disease (primary or in relapse)
  * 2nd or greater relapse
  * Any relapse after allogeneic hematopoietic cell transplantation
  * 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

    * must be confirmed to be CD19+ within 3 months prior to enrollment for treatment
* Age: ≤ 21 years of age
* Karnofsky or Lansky (age-dependent) performance score ≥ 50 (Appendix A)
* Estimated life expectancy of \> 12 weeks. Patients with a history of prior allogeneic hematopoietic cell transplantation \[HCT\] must be clinically recovered from prior HCT therapy, have no evidence of active GVHD and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis
* For females of child bearing age:

  * Not lactating with intent to breastfeed
  * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment

Exclusion Criteria:

* Known primary immunodeficiency
* History of HIV infection
* Severe intercurrent bacterial, viral or fungal infection
* History of hypersensitivity reactions to murine protein-containing products
* Known contraindication to receiving protocol defined lymphodepleting chemotherapy regimen

Treatment

Inclusion Criteria:

* Age: ≤ 21 years of age
* Estimated life expectancy of \> 8 weeks
* Detectable disease
* Prior to planned CAR T cell infusion, patients with a history of prior allogeneic HCT must:

  * be at least 3 months from HCT
  * have no evidence of active GVHD
  * have not received a donor lymphocyte infusion (DLI) within the 28 days prior to planned infusion
* Adequate cardiac function defined as left ventricular ejection fraction \> 40%, or shortening fraction ≥ 25%
* EKG without evidence of clinically significant arrhythmia
* Adequate renal function defined as creatinine clearance or radioisotope GFR ³ 50 ml/min/1.73m2 (GFR ³ 40 ml/min/1.73m2 if \< 2 years of age)
* Adequate pulmonary function defined as forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing
* Karnofsky or Lansky (age-dependent) performance score ≥ 50 (Appendix A)
* 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
* Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy
* For patients of child bearing age:

  * Not lactating with intent to breastfeed
  * Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
  * If sexually active, agreement to use birth control until 6 months after T cell infusion.

Exclusion Criteria:

* Active CNS-3 disease
* Known primary immunodeficiency
* History of HIV infection
* Evidence of active, uncontrolled neurologic disease
* Severe, uncontrolled bacterial, viral or fungal infection
* History of hypersensitivity reactions to murine protein-containing products
* Known contraindication to receiving protocol defined lymphodepleting chemotherapy regimen

Where this trial is running

Memphis, Tennessee

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

Study contacts

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

Conditions: Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia