Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia
Conditions
Brief 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.
Detailed description
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.
Interventions
DRUGFludarabine
Given IV
DRUGCyclophosphamide
Given IV
DRUGMesna
Given IV
BIOLOGICALCD19-CAR T cell Infusion
Patients will receive the CD19-CAR T cells by vein, through either an IV or a central line.
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fludarabine Pharmacokinetics | Days -5, -4 and -3 | Determination of Fludarabine exposure (area under the curve \[AUC\], mg-hr/L) using blood samples collected on days -5, -4 and -3 |
Countries
United States
Contacts
CONTACTAimee Talleur, MD
PRINCIPAL_INVESTIGATORAimee Talleur, MD
St. Jude Children's Research Hospital
Outcome results
None listed