CART19 in Adult Patients With Minimal Residual Disease During Upfront Treatment for ALL

Study Overview
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Brief Summary
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This is a single center, single arm, open-label phase 2 study to determine the efficacy of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as CART19 cells) in adults with minimal residual disease (MRD) during upfront treatment for CD19+ acute lymphoblastic leukemia.

Official Title
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Phase 2 Study of CD19-directed Chimeric Antigen Receptor-modified T Cells (CART19) for Adult Patients With Minimal Residual Disease During Upfront Treatment for Acute Lymphoblastic Leukemia

Conditions
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Leukemia, Acute Lymphoblastic

Intervention / Treatment
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* Biological: CART 19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CD19+, B cell Acute Lymphoblastic Leukemia (B-ALL) who have 0.01%≤MRD<10% during upfront treatment Patients must be within 18 months of initial ALL diagnosis Age ≥18 years Adequate organ function defined as: Creatinine ≤ grade 2 ALT/AST ≤3x upper limit of normal range for age Direct bilirubin ≤2.0 mg/dl Adequate pulmonary function defined as ≤ grade 2 dyspnea and ≤ grade 2 hypoxia Cardiac Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy. Expression of CD19 on leukemic blasts demonstrated by flow cytometry or immunohistochemistry of bone marrow or peripheral blood Adequate performance status defined as ECOG Performance Status 0 or 1 Provides written informed consent Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Exclusion Criteria: Active, uncontrolled infection Active hepatitis B or hepatitis C HIV Infection Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 2) Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of enrollment. Pregnant or nursing (lactating) women Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment.

Ages Eligible for Study
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Minimum Age: 18 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: CART19<br>CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion. | Biological: CART 19<br>* CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion. Subjects will receive 1-5 x 10^8 transduced CAR T cells as a split dose over three days as follows:Day 1, 10% fraction: 1-5x10^7 CART19 cells, Day 2, 30% fraction: 3x10^7-1.5x10^8 CART19 cells, Day 3, 60% fraction: 6x10^7-3x10^8 CART19 cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Conversion of Minimal Residual Disease (MRD) to <0.01% | The incidence of conversion of minimal residual disease (MRD) to <0.01% after CART19 therapy in patients with MRD+ ALL during upfront treatment | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Survival (OS) | Overall survival (OS) is defined as the time from the date of the first CART19 infusion to the date of death due to any reason. | one year | 
| Duration of Remission (DOR) | Duration of remission (DOR) is defined as the duration from the date when the response criteria of CR or CRi is first met to the date of relapse or death due to ALL. | one year | 
| Relapse Free Survival (RFS) | Relapse free survival (RFS) is defined as the duration between the date when the response criteria of CR or CRi is first met to the date of relapse or death due to any cause. | one year | 
| Event Free Survival (EFS) | Event free survival (EFS) is defined as the time from start of the first CART19 infusion to the earliest of the following: Death from any cause Relapse Treatment failure: Defined as no response in the study and discontinuation from the study due to any of the following reasons: Adverse event(s) Abnormal laboratory value(s) Abnormal test procedure results New cancer therapy (excluding HSCT when performed in CR or CRi) | one year | 
| Percentage of Manufacturing Products That do Not Meet Release Criteria for Vector Transduction Efficiency, T Cell Product Purity, Viability, Sterility or Due to Tumor Contamination. | Percentage of manufacturing products that do not meet release criteria for vector transduction efficiency, T cell product purity, viability, sterility or due to tumor contamination. | prior to day 1 | 
| Safety and Tolerability of CART19: Frequency and Severity of Adverse Events, Including, But Not Limited to, Cytokine Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS). | Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) and macrophage activation syndrome (MAS). | one year |