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