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

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.

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