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Phase I/IIA Study of CART19 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma

NCT01626495

Description:

This is a study for children who have been previously treated for Leukemia/Lymphoma. In particular, it is a study for people who have a type of Leukemia/Lymphoma that involves B cells (a type of white cell), which contain the cancer. This is a new approach for treatment of Leukemia/Lymphoma that involves B cells (tumor cells). This study will take the subject's white blood cells (T cells) and modify them in order to target the cancer. The subject's T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells). Both ways of modifying the cells tells the T cells to go to the B cells (tumor cells) and turn "on" and potentially kill the B cells (tumor cells). The modification is a genetic change to the T cells, or gene transfer, in order to allow the modified T cells to recognize your tumor cells but not other normal cells in the subject's body. These modified cells are called chimeric antigen receptor 19 (CART19) T-cells.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Mature B-Cell Lymphoma/Leukemia
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Phase I/IIA Study of CART19 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ <span class="go-doc-concept go-doc-disease">Leukemia</span> and <span class="go-doc-concept go-doc-disease">Lymphoma</span>

Title

  • Brief Title: Phase I/IIA Study of CART19 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma
  • Official Title: CHP 959 - A Phase I/IIA Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRzeta and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant Or Refractory CD19+ Leukemia and Lymphoma
  • Clinical Trial IDs

    NCT ID: NCT01626495

    ORG ID: 10-007706

    NCI ID: CHP-959

    Trial Conditions

    B Cell Leukemia

    B Cell Lymphoma

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This is a study for children who have been previously treated for Leukemia/Lymphoma. In
    particular, it is a study for people who have a type of Leukemia/Lymphoma that involves B
    cells (a type of white cell), which contain the cancer. This is a new approach for treatment
    of Leukemia/Lymphoma that involves B cells (tumor cells). This study will take the subject's
    white blood cells (T cells) and modify them in order to target the cancer.

    The subject's T cells will be modified in one or two different ways that will allow the
    cells to identify and kill the tumor cells (B cells). Both ways of modifying the cells tells
    the T cells to go to the B cells (tumor cells) and turn "on" and potentially kill the B
    cells (tumor cells). The modification is a genetic change to the T cells, or gene transfer,
    in order to allow the modified T cells to recognize your tumor cells but not other normal
    cells in the subject's body. These modified cells are called chimeric antigen receptor 19
    (CART19) T-cells.

    Detailed Description

    At entry subjects will be staged and the suitability of their T cells for CART-19
    manufacturing will be determined. Subjects who have adequate T cells will be leukapheresed
    to obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-19
    manufacturing. The T cells will be purified from the PBMC, transduced with CART-19
    lentiviral vector, expanded in vitro and then frozen for future administration. Chemotherapy
    will then be given. Following tumor burden reassessment, CART-19 cells will be thawed and
    infused.

    Subjects will have blood tests to assess safety, and engraftment and persistence of the
    CART-19 cells at regular intervals through four weeks after their last infusion of the
    study. Following the 6 months of intensive follow-up, subjects will be evaluated quarterly
    for two years with a medical history, a physical examination, and blood tests. Following
    this evaluation, subjects will enter a roll-over study for annual follow-up by phone and
    questionnaire for an additional thirteen years to assess for the diagnosis of long-term
    health problems, such as development of new malignancy.

    Primary objectives:

    1. Determine the safety and feasibility of administration of chimeric antigen receptor T
    cells transduced with the anti-CD 19 lentiviral vector (referred to as "CART-19"
    cells).

    2. Determine duration of in vivio survival of CART-19 cells. Real Time polymerase chain
    receptor (RT-PCR) analysis of whole blood will be used to detect and quantify survival
    of CART-19 TCR:4-1BB and TCR cells over time.

    Secondary objectives:

    1. For patients with detectable disease, measure anti-tumor response due to CART-19 cell
    infusions.

    2. To determine if the 4-1BB transgene is superior to the TCR only transgene as measured
    by the relative engraftment levels of CART-19 TCR:4-1BB and TCR cells over time.

    3. For patients with stored or accessible tumor cells (such as patients with active
    chronic lymphocytic leukemia (CLL), acute lymphoblastic leukema (ALL), etc) determine
    tumor cell killing by CART-19 cells in vitro.

    4. Determine if cellular or humoral host immunity develops against the murine anti-CD19,
    and assess correlation with loss of detectable CART-19 (loss of engraftment).

    5. Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg)

    Trial Arms

    Name Type Description Interventions
    CART-19 T Cells Experimental The subject's thawed T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells). The T cells will be infused over 10-15 minutes on days Days 0, and 1. Day 14 is tentative based on response.

    Eligibility Criteria

    Inclusion Criteria:

    Male and female subjects with CD19+ B cell malignancies 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:

    1. Eligible diseases: CD19+ leukemia or lymphoma

    a. ALL without curative options for therapy, including those not eligible for
    allogeneic SCT because of: i. age ii. comorbid disease iii. other contraindications
    to TBI-based conditioning (required for ALL SCT) iv. lack of suitable donor v. prior
    SCT vi. Declines allo SCT (in CR3) as a therapeutic option after documented
    discussion about the role of SCT with a BMT physician not part of the study team

    . Patient may be in any complete response, or patient may have active disease but
    responding or stable after most recent therapy. The intent is not to enroll patients
    with no degree of disease control, or rapidly increasing disease burden between
    enrollment and cell infusion.

    b. Diffuse large cell lymphoma or other high-grade NHL, previously identified as
    CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT.
    ii. Relapsed after prior autologous SCT. iii. Beyond 1st CR with relapsed or
    persistent disease and not eligible or appropriate for conventional allogeneic or
    autologous SCT.

    2. Age 1 to 24 years. Patients ages 22-24 will only be enrolled if they are currently
    being treated at CHOP or another pediatric facility/oncologist.

    3. Expected survival > 12 weeks

    4. Creatinine < 2.5 mg/dl and less than 2.5x normal for age

    5. ALT <= 5x normal

    6. Bilirubin <2.0 mg/dl

    7. Any relapse after prior SCT will make patient eligible regardless of other prior
    therapy.

    8. 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 (6 months at infusion)

    9. 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.

    10. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.

    10. Voluntary informed consent is given.

    Exclusion Criteria:

    1. 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.

    2. Uncontrolled active infection.

    3. Active hepatitis B or hepatitis C infection.

    4. 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.

    5. Presence of grade 2-4 acute or extensive chronic GVHD.

    6. Under treatment for GVHD.

    7. Previous treatment with any gene therapy products.

    8. Feasibility assessment during screening shows insufficient expansion in response to
    CD3/CD28 costimulation.

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

    10. HIV infection.

    11. Patients with active CNS involvement with malignancy (i.e. CNS3 for ALL). Patients
    with prior CNS disease that has been effectively treated will be eligible. Routine
    CNS prophylaxis for ALL is permitted.

    Minimum Eligible Age: 1 Year

    Maximum Eligible Age: 24 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability

    Secondary Outcome Measures

    Ability of two different types of CAR+ T cells to expand and persist in the patient

    Impact of CAR+ T cell infusion on cancer

    Trial Keywords

    Biological: CART19