CART19 in Adult Patients With Minimal Residual Disease During Upfront Treatment for ALL
Condition: Leukemia, Acute Lymphoblastic
MeSH terms: Leukemia; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Intervention: CART 19
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with CD19+, B cell Acute Lymphoblastic Leukemia (B-ALL) who have
             0.01%≤MRD<10% during upfront treatment

          2. Patients must be within 18 months of initial ALL diagnosis

          3. Age ≥18 years

          4. Adequate organ function defined as:

               1. Creatinine ≤ grade 2

               2. ALT/AST ≤3x upper limit of normal range for age

               3. Direct bilirubin ≤2.0 mg/dl

               4. Adequate pulmonary function defined as ≤ grade 2 dyspnea and ≤ grade 2 hypoxia

               5. Cardiac Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA

          5. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.

          6. Expression of CD19 on leukemic blasts demonstrated by flow cytometry or
             immunohistochemistry of bone marrow or peripheral blood

          7. Adequate performance status defined as ECOG Performance Status 0 or 1

          8. Provides written informed consent

          9. Subjects of reproductive potential must agree to use acceptable birth control methods,
             as described in protocol

        Exclusion Criteria:

          1. Active, uncontrolled infection

          2. Active hepatitis B or hepatitis C

          3. HIV Infection

          4. Class III/IV cardiovascular disability according to the New York Heart Association
             Classification (see Appendix 2)

          5. Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on
             medical management within two weeks of enrollment.

          6. Pregnant or nursing (lactating) women

          7. 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.