CAR T CELL Therapy for Pediatric, Adolescent and Young Adult Patients With CD19-Positive Leukemia

Sponsor: St. Jude Children's Research Hospital

Sponsor score: 60

ClinicalTrials ID:NCT06847269

CAR19PK is a Phase II study for patients ≤ 21 with relapsed/refractory CD19+ leukemia. It involves lymphodepleting chemotherapy (fludarabine, cyclophosphamide) followed by CD19-CAR T cell infusion. Eligible participants must have a performance score ≥ 50 and life expectancy > 12 weeks. Interventions include IV fludarabine, cyclophosphamide, mesna, and CD19-CAR T cell infusion.

Patient Parameters

Program Overview

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.

Description

CAR19PK is a Phase II study evaluating lymphodepleting chemotherapy (age-based fludarabine dosing and cyclophosphamide), followed by infusion of CD19-CAR T cells, in pediatric and young adult patients ≤ 21 years old with relapsed/refractory CD19-positive leukemia. Treatment will include a single course of lymphodepleting chemotherapy followed by CAR T cell infusion. Lymphodepletion will include fludarabine (dosing based on age) and cyclophosphamide. The CAR T cell infusion will include a single infusion of 3x10^6 CD19-CAR T cells/kg patient weight.

This protocol contains a two-part consent process: 1) to proceed with autologous apheresis and 2) to proceed with treatment with lymphodepleting chemotherapy and infusion of the CD19-CAR T cell product.

Eligibility Criteria

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

Locations

FACILITYZIPCITYSTATE
St. Jude Children's Research Hospital38105MemphisTennessee

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