Evaluation of CD19-Specific CAR Engineered Autologous T-Cells for Treatment of Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia

Inclusion Criteria for Autologous Apheresis:

• Age ≤ 21 years old

• CD19+ ALL with any of the following:

  • Minimal Residual Disease (MRD) ≥ 1% at end of up-front induction therapy
  • Hypodiploid (< 44 chromosomes or < 0.95 DNA index) CD19+ ALL with detectable disease at the end of up-front induction therapy
  • Increase in disease burden any time after the completion of up-front induction therapy
  • Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission
  • Refractory disease despite salvage therapy
  • 1st or greater relapse
• Estimated life expectancy of > 12 weeks
• Karnofsky or Lansky (age-dependent) performance score ≥ 50
• 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 for Autologous Apheresis:

• Known primary immunodeficiency
• History of HIV infection
• Severe intercurrent bacterial, viral or fungal infection
• History of hypersensitivity reactions to murine protein-containing products

Eligibility Criteria for Manufacturing SJCAR19:

• CD19+ ALL with any of the following:

  • Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission
  • Refractory disease despite salvage therapy
  • 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
• Age: ≤ 21 years of age
• Karnofsky or Lansky (age-dependent) performance score ≥ 50
• Estimated life expectancy of > 12 weeks
• Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis

Inclusion Criteria for Treatment with SJCAR19:

• CD19+ ALL with any of the following:

  • Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission
  • Refractory disease despite salvage therapy
  • 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 for any of the following reasons:

    • Patients that do not have an available allogeneic donor (defined as at least a 7/8 HLA-matched related/unrelated donor, 5/6 HLA-matched umbilical cord donor, or 3/6 HLA-matched haploidentical donor)
    • Patients with refractory leukemia, for which allogeneic transplant is known to be less effective in the B-ALL population, and
    • Patients who are unable to receive myeloablative total body irradiation (TBI), which is included in standard transplant regimens for patients with B - ALL.
• Detectable disease
• Age: ≤ 21 years of age
• Estimated life expectancy of > 8 weeks
• Prior to planned SJCAR19 infusion, patients with a history of prior allogeneic HCT must be at least 3 months from HCT, have no evidence of active GVHD and 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 ≥50 ml/min/1.73m2 (GFR ≥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
• 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
• Hemoglobin > 8 g/dl (can be transfused)
• Platelet count > 20,000/μL (can be transfused)
• Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy

• 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
  • If sexually active, agreement to use birth control until 6 months after T-cell infusion. Male partners should use a condom
• Available SJCAR19 product with ≥ 15% expression of the CD19-CAR, and killing of CD19+ targets ≥ 20% in an in vitro cytotoxicity assay
• Agreement to participate in long-term follow-up on protocol NCT00695279

Exclusion Criteria for Treatment with SJCAR19:

• CNS-3 disease with or without neurologic changes
• CNS-1/CNS-2 disease with neurologic changes
• 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
• Receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/ kg/day of methylprednisolone, in the 7 days prior to CAR T-cell infusion
• Receiving systemic immunosuppressive therapy in the 14 days prior to CAR T-cell infusion
• Receiving intrathecal chemotherapy in the 7 days prior to CAR T-cell infusion