Clinical Trials /

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

NCT02935543

Description:

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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:CART19 in Patient With ALL
  • Official Title: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

Clinical Trial IDs

  • ORG STUDY ID: 825668
  • NCT ID: NCT02935543

Trial Conditions

  • Leukemia, Acute Lymphoblastic

Trial Interventions

DrugSynonymsArms

Trial Purpose

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.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
CART19ExperimentalCART19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRz:41BB administered by IV infusion.

    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.

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:The incidence of conversion of minimal residual disease (MRD) to <0.01% after CART19 therapy in patients with MRD+ ALL during upfront treatment
    Time Frame:Day 28
    Safety Issue:No
    Description:

    Secondary Outcome Measures

    Measure:Best overall survival (OS),
    Time Frame:one year
    Safety Issue:No
    Description:
    Measure:Duration of remission (DOR) ,
    Time Frame:one year
    Safety Issue:No
    Description:
    Measure:Relapse free survival (RFS)
    Time Frame:one year
    Safety Issue:No
    Description:
    Measure:Event free survival (EFS)
    Time Frame:one year
    Safety Issue:No
    Description:
    Measure: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.
    Time Frame:prior to day 1
    Safety Issue:No
    Description:
    Measure:Frequency and severity of adverse events
    Time Frame:one year
    Safety Issue:Yes
    Description:

    Trial Keywords