Overview
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.
Description
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.
Eligibility
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-containing products
Treatment Eligibility
Inclusion Criteria:
- Age < 21 years old
- Detectable CD19- and/or CD22-positive leukemic 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