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

Phase 2

Recruiting

• Conditions: Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Mesna; Biological: CD19-CAR T cell Infusion

• Registration Number: NCT06847269
• Lead Sponsor: St. Jude Children's Research Hospital

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2025-02-21
• Study First Submitted QC: 2025-02-21
• Study First Posted: 2025-02-26
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-21
• Last Update Posted: 2025-05-22
• Study Start: 2025-08
• Primary Completion: 2030-03
• Study Completion: 2031-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR19PK Therapy	Fludarabine	This study contains two phases. Collection and Manufacturing Phase: Patient blood cells will be collected, and possibly frozen, via a process called apheresis. These cells will then be changed to improve their ability to recognize and kill cancer cells. Treatment Phase: Patients that meet eligibility for treatment will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by an infusion of CD19-CAR T cells that were made in the Collection and Manufacturing Phase.
CAR19PK Therapy	Cyclophosphamide	This study contains two phases. Collection and Manufacturing Phase: Patient blood cells will be collected, and possibly frozen, via a process called apheresis. These cells will then be changed to improve their ability to recognize and kill cancer cells. Treatment Phase: Patients that meet eligibility for treatment will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by an infusion of CD19-CAR T cells that were made in the Collection and Manufacturing Phase.
CAR19PK Therapy	Mesna	This study contains two phases. Collection and Manufacturing Phase: Patient blood cells will be collected, and possibly frozen, via a process called apheresis. These cells will then be changed to improve their ability to recognize and kill cancer cells. Treatment Phase: Patients that meet eligibility for treatment will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by an infusion of CD19-CAR T cells that were made in the Collection and Manufacturing Phase.
CAR19PK Therapy	CD19-CAR T cell Infusion	This study contains two phases. Collection and Manufacturing Phase: Patient blood cells will be collected, and possibly frozen, via a process called apheresis. These cells will then be changed to improve their ability to recognize and kill cancer cells. Treatment Phase: Patients that meet eligibility for treatment will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by an infusion of CD19-CAR T cells that were made in the Collection and Manufacturing Phase.

Primary Outcome Measures

Name	Time	Method
Fludarabine Pharmacokinetics	Days -5, -4 and -3	Determination of Fludarabine exposure (area under the curve \[AUC\], mg-hr/L) using blood samples collected on days -5, -4 and -3

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States