This study is a phase I study designed to evaluate the safety of CD19-CD22-CAR T cells.

Primary Objective:

To determine the safety profile and propose the recommended phase 2 dose (RP2D) of autologous CD19-CD22-CAR T cells in patients ≤ 21 years of age with recurrent/refractory CD19- and/or CD22-positive leukemia.

Secondary Objective:

To evaluate the anti-leukemic activity of CD19-CD22-CAR T cells.

Treatment will include a single course of lymphodepleting chemotherapy (fludarabine/cyclophosphamide) followed by CAR T cell infusion. CAR T cell dose will be determined by the protocol-defined dose escalation scheme, based on the number of CAR+ T cells and participant weight.

Collection and Manufacturing Eligibility

Inclusion Criteria:

• Age <21 years old

• Relapsed/refractory CD19- and/or CD22-positive acute leukemia defined as:

  *CD19 and/or CD22-positivity confirmed within 2 months and after receipt of any CD19 or CD22-directed therapy

  • Second or greater relapse
  • Any relapse after allogeneic HCT
  • Refractory disease (primary or in relapse) despite therapy designed to induce remission

• Estimated life expectancy of > 12 weeks

• Karnofsky or Lansky (age-dependent) performance score ≥50 (Appendix A)

• For females of childbearing age:

  • Not lactating with intent to breastfeed
  • Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment

Exclusion Criteria:

• Known primary immunodeficiency
• Known HIV positivity
• Known contraindication to receiving protocol defined lymphodepleting
• chemotherapy regimen
• History of hypersensitivity reaction to murine protein-containing products

Treatment Eligibility

Inclusion Criteria:

• Age < 21 years old

• Detectable disease in the bone marrow

• Estimated life expectancy of > 8 weeks

• Karnofsky or Lansky (age-dependent) performance score > 50 (Appendix A)

• 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

• 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

• Prior to planned CAR T cell infusion, patients with a history of prior allogeneicHCT must be at least 3 months from HCT, have no evidence of acute GVHD, and have not received a donor lymphocyte infusion (DLI) within the 28 daysprior to planned infusion

• For females of childbearing age:

  • Not lactating with intent to breastfeed
  • Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment
  • If sexually active, agreement to use birth control until 3 months after T cell infusion. Male partners should use a condom.

Exclusion Criteria:

• Known primary immunodeficiency
• Known HIV positivity
• Known contraindication to receiving protocol defined lymphodepleting
• chemotherapy regimen
• History of hypersensitivity reactions to murine protein-containing products
• Severe, uncontrolled bacterial, viral or fungal infection
• Active CNS-3 disease
• Evidence of active, uncontrolled neurologic disease