Clinical Trials /

Dose Optimization Trial of CD19 Redirected Autologous T Cells

NCT01747486

Description:

This is a randomized, open-label, parallel group study to determine the optimal dose of CART-19 cells (autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR Zeta and 4-1 BB co-stimulatory domains) of the two dose levels being assessed (1-5x10e8 vs. 1-5x10e7 CART-19 cells). This trial will be conducted in two stages.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

CD19 Redirected Autologous T Cells

Title

  • Brief Title: CD19 Redirected Autologous T Cells
  • Official Title: Dose Optimization Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART-19) in Patients With Relapsed or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)
  • Clinical Trial IDs

    NCT ID: NCT01747486

    ORG ID: UPCC 03712

    Trial Conditions

    Adult Patients Who Have Relapsed or Refractory CLL (3rd Line) or SLL

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This is a randomized, open-label, parallel group study to determine the optimal dose of
    CART-19 cells (autologous T cells expressing CD19 chimeric antigen receptors expressing
    tandem TCR Zeta and 4-1 BB co-stimulatory domains) of the two dose levels being assessed
    (1-5x10e8 vs. 1-5x10e7 CART-19 cells). This trial will be conducted in two stages.

    Detailed Description

    This study is being conducted to determine the optimal dose of autologous CART-19 T cells
    engineered to express anti-CD19 chimeric antigen receptors in patients with relapsed or
    refractory CD19 positive chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma
    (SLL). The two dose levels being assessed are 1-5x10e8 versus 1-5x10e7. The trial will be
    conducted in two stages. In stage I subjects will be randomized into one of the two dose
    cohort with a1:1 ratio for a total of 12 subjects per dose cohort. Stage II will be to
    enroll an additional 8 subjects to the selected dose cohort once safety, tolerability and
    clinical responses have been evaluated to determine the optimal dose cohort.

    Trial Arms

    Name Type Description Interventions
    Target dose of 1-5x10e8 Experimental Arm 1: Target dose of 1-5x10e8 CART-19 cells (calculated as range of 10-50% transduced cells in 1 x10e9 total cells)
    Target dose of 1-5x10e7 Experimental Arm 2: Target dose of 1-5x10e7 CART-19 cells (calculated as the range of 10-50% transduced cells in 1 x10e8 total cells)

    Eligibility Criteria

    Inclusion Criteria:

    - Documented CD19+ CLL or SLL

    - Successful test expansion of T-cells

    - At least 2 prior chemotherapy regimens, not including single agent monoclonal
    antibody (rituximab) therapy. Single agent ofatumumab will be counted as a regimen.
    Patients with high risk disease, manifested by deletion chromosome 17p, will be
    eligible if they fail to achieve a CR to initial therapy or progress within 2 years
    of 1 prior regimen

    - Patients who progress within 2 years after the second or higher line of therapy will
    be eligible. For instance, patients who had progression greater than 2 years after
    second or greater line therapy, but who have responded to their most recent treatment
    (3rd line or higher) will be eligible

    - Subject is not appropriate candidate for a potentially curative allogeneic SCT due to
    the state of disease, co-morbid illness, lack of an available donor, or patient
    declines

    - Expected survival greater than 12 weeks.

    - Performance status (ECOG) 0 or 1

    - Age greater than or equal to 18 years

    - Adequate organ system function including:

    1. Creatinine less than 1.6 mg/dl

    2. ALT/AST less than 3x upper limit of normal

    3. Direct Bilirubin less than 2.0 mg/dl 10) Any relapse after prior autologous SCT
    will make patient eligible regardless of other prior therapy

    - Patients with relapsed disease after prior allogeneic SCT (myeloablative or
    nonmyeloablative) will be eligible if they meet all other inclusion criteria and:

    1. experienced graft rejection (no evidence of donor cells by STR analysis on 2
    occasions separated by at least 1 month)

    2. Have no active GVHD and require no immunosuppression

    3. Are more than 6 months from transplant

    - No contraindications for leukapheresis

    - Left ventricular Ejection Fraction greater than 40% 14) Gives voluntary informed
    consent Retreatment Cohort: Up to one retreatment dose will be allowed per eligible
    subject.

    - Subjects previously infused with CART19 cells as part of this protocol and who
    experienced an initial response (either CR, CRi or PR) to therapy, but have
    subsequently progressed within 2 years of their initial response. - - Subjects have
    undergone the 3 month efficacy endpoint evaluation. Subjects who achieve an initial
    response, but relapse prior to this Month 3 timepoint will be eligible.

    - Subjects have less than 5% CART19 cells in the CD3+ population by flow cytometry on
    PBMCs

    - Subjects have recovered from any toxicity attributed to the initial CART19 infusion,
    such as CRS. In addition, subjects must also meet the following:

    - Performance Status 0-1

    Adequate organ system function including:

    Creatinine less than1.6 mg/dl -ALT/AST less than 3x upper limit of normal Total Bilirubin
    less than 2.0 mg/dl

    - Subject is not an appropriate candidate for a potentially curative allogeneic SCT due
    to the state of disease, co-morbid illness, lack of an available donor, or patient
    declines.

    - Expected survival greater than 12 weeks

    - Left Ventricular Ejection Fraction greater than 40percent

    - No contraindications for leukapheresis (if required for retreatment)

    - Gives voluntary informed consent for retreatment

    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 or chronic use of immunosuppressant medications.
    Recent or current use of inhaled steroids is not exclusionary. For additional details
    regarding use of steroid and immunosuppressant medications.

    - Any uncontrolled active medical disorder that would preclude participation as
    outlined

    - HIV infection

    - Patients with active CNS involvement with malignancy. Patients with prior CNS disease
    that has been effectively treated will be eligible providing treatment was 4 weeks
    before enrollment.

    - Class III/IV cardiovascular disability according to the New York Heart Association
    Classification.

    Retreatment Exclusion Criteria

    - Pregnant or lactating women. Female study participants must have a negative serum or
    urine pregnancy test performed within 48 hours before infusion. - Uncontrolled active
    infection

    - Active hepatitis or hepatitis infection

    - Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not
    exclusionary.

    - Any uncontrolled active medical disorder that would preclude participation as
    outlined.

    - HIV infection

    - Patients with active CNS involvement with malignancy. Patients with prior CNS disease
    that has been effectively treated will be eligible providing treatment was greater
    than 4 weeks before enrollment on the retreatment cohort.

    - Class III/IV cardiovascular disability according to the New York Heart Association
    Classification

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of Adverse Events

    Secondary Outcome Measures

    Trial Keywords