CD19-CD22-Bispecific Chimeric Antigen Receptor (CAR) T Cell Therapy for Pediatric Patients With Acute Lymphoblastic Leukemia

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