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

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