Efficacy of CART-19 Cell Therapy in B Cell Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is a single arm, open-label, multi-center study to determine the efficacy and safety of an experimental therapy called CART-19 in patients with chemo-refractory and relapsed B-cell ALL.

Detailed Description
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This is a single arm, open-label, multi-center, phase I study to determine the efficacy of CTL019 in patients with r/r B-cell ALL. The study will have the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation & Lymphodepleting Chemotherapy), Treatment and Primary Follow-up, Secondary Follow-up (if applicable) and Survival Follow-up.

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Biological: CART-19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects with CD 19+ B cell acute lymphoblastic leukemia in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to <2 year survival) with currently available therapies will be enrolled Age 1 to 60 years. Expected survival > 12 weeks Creatinine < 2.5 mg/dl and less than 2.5x normal for age ALT ≤ 5x normal Bilirubin <2.0 mg/dl Any relapse after prior SCT will make patient eligible regardless of other prior therapy Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and ①. Have no active GVHD and require no immunosuppression ②. Are more than 4 months from transplant For those patients who require leukapheresis for T cell collection (i.e. no previously collected product exists), adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis Voluntary informed consent is given Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion) Exclusion Criteria: Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion Uncontrolled active infection Active hepatitis B or hepatitis C infection Concurrent use of systemic steroids at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of inhaled steroids, or hydrocortisone for physiological replacement in patients with adrenal insufficiency are permitted as well Presence of grade 2-4 acute or extensive chronic GVHD Under treatment for GVHD Previous treatment with any gene therapy products Any uncontrolled active medical disorder that would preclude participation as outlined. HIV infection. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose of CART-19<br>2 to 5 x 10(6) autologous CART-19 transduced cells per kg body weight, with a maximum dose of 2.5 x 10(8) autologous CTL019 transduced cells via intravenous infusion. | Biological: CART-19<br>* 2 to 5 x 10(6) autologous CART-19 transduced cells per kg body weight, with a maximum dose of 2.5 x 10(8) autologous CTL019 transduced cells via intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events |  | 2 years |