RecruitingPhase 2NCT06847269

CAR T CELL Therapy for Pediatric, Adolescent and Young Adult 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


Sponsor

St. Jude Children's Research Hospital

Enrollment

25 participants

Start Date

May 21, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

CAR19PK is a research study evaluating the use of lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T cell therapy, a type of cellular therapy, for the treatment of refractory and/or relapsed leukemia. For this type of therapy, peripheral (circulating) immune cells are collected and then modified so that they can recognize an antigen, which is a particle present on the surface of a cancer cell. The CD19-CAR T cell product will be manufactured at the St. Jude Children's Research Hospital's Good Manufacturing Practice (GMP) facility. The main purpose of this study is to determine: * Evaluate different doses of fludarabine prior CAR T cell infusion * How your body processes fludarabine and cyclophosphamide, * How long the CAR T cells last in the body, * Whether or not treatment with this therapy is effective in treating people with refractory or relapsed leukemia, and * The side effects of this therapy.


Eligibility

Max Age: 21 Years

Inclusion Criteria32

  • Autologous Apheresis and Manufacturing
  • CD19+ leukemia\*\* with any of the following:
  • Refractory disease (primary or in relapse)
  • nd or greater relapse
  • Any relapse after allogeneic hematopoietic cell transplantation
  • st 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
  • 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 Criteria13

  • 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
  • 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

Interventions

DRUGFludarabine

Given IV

DRUGCyclophosphamide

Given IV

DRUGMesna

Given IV

BIOLOGICALCD19-CAR T cell Infusion

Patients will receive the CD19-CAR T cells by vein, through either an IV or a central line.


Locations(1)

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

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NCT06847269


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