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
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