cd19-cd22-bispecific chimeric antigen receptor (car) t cell therapy for pediatric patients with acute lymphoblastic leukemia

Conditions: Acute Lymphoblastic Leukemia; Recurrent Acute Lymphoblastic Leukemia; Recurrent B Acute Lymphoblastic Leukemia

Summary: 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.

Eligibility criteria:
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