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

Official title

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

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.

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.

Interventions

• Drug Fludarabine
  Given IV
• Drug Cyclophosphamide
  Given IV
• Drug Mesna
  Given IV
• Biological CD19-CAR T cell Infusion
  Patients will receive the CD19-CAR T cells by vein, through either an IV or a central line.

Primary outcome measures

• Fludarabine Pharmacokinetics [Time frame: Days -5, -4 and -3]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• St. Jude Children's Research Hospital — Memphis

Identifiers

NCT: NCT06847269 · CAR19PK

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗