car t cell therapy for pediatric, adolescent and young adult patients with cd19-positive leukemia

Conditions: Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia

Summary: car19pk is a research study evaluating the use of lymphodepleting chemotherapy and chimeric antigen receptor (car) t cell therapy, a type of cellular therapy, for the treatment of refractory and/or relapsed leukemia. for this type of therapy, peripheral (circulating) immune cells are collected and then modified so that they can recognize an antigen, which is a particle present on the surface of a cancer cell. the cd19-car t cell product will be manufactured at the st. jude children's research hospital's good manufacturing practice (gmp) facility. the main purpose of this study is to determine: * evaluate different doses of fludarabine prior car t cell infusion * how your body processes fludarabine and cyclophosphamide, * how long the car t cells last in the body, * whether or not treatment with this therapy is effective in treating people with refractory or relapsed leukemia, and * the side effects of this therapy.

car19pk is a phase ii study evaluating lymphodepleting chemotherapy (age-based fludarabine dosing and cyclophosphamide), followed by infusion of cd19-car t cells, in pediatric and young adult patients ≤ 21 years old with relapsed/refractory cd19-positive leukemia. treatment will include a single course of lymphodepleting chemotherapy followed by car t cell infusion. lymphodepletion will include fludarabine (dosing based on age) and cyclophosphamide. the car t cell infusion will include a single infusion of 3x10\^6 cd19-car t cells/kg patient weight. this protocol contains a two-part consent process: 1) to proceed with autologous apheresis and 2) to proceed with treatment with lymphodepleting chemotherapy and infusion of the cd19-car t cell product.

Eligibility criteria:
autologous apheresis and manufacturing inclusion criteria: * cd19+ leukemia\*\* with any of the following: * refractory disease (primary or in relapse) * 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 * must be confirmed to be cd19+ within 3 months prior to enrollment for treatment * age: ≤ 21 years of age * karnofsky or lansky (age-dependent) performance score ≥ 50 (appendix a) * estimated life expectancy of \> 12 weeks. 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: * known primary immunodeficiency * history of hiv infection * severe intercurrent bacterial, viral or fungal infection * history of hypersensitivity reactions to murine protein-containing products * known contraindication to receiving protocol defined lymphodepleting chemotherapy regimen treatment inclusion criteria: * age: ≤ 21 years of age * estimated life expectancy of \> 8 weeks * detectable disease * prior to planned car t cell infusion, patients with a history of prior allogeneic hct must: * be at least 3 months from hct * have no evidence of active gvhd * 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 ³ 50 ml/min/1.73m2 (gfr ³ 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 (appendix a) * 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 * for patients 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. exclusion criteria: * active cns-3 disease * 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 * known contraindication to receiving protocol defined lymphodepleting chemotherapy regimen