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PR1-Specific Cytotoxic T-Lymphocyte Infusion With Recurrent Chronic Myelogenous Leukemia (CML) After Allogeneic Hematopoietic Transplantation

Primary Purpose

Chronic Myelogenous Leukemia

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
PR1-primed lymphocyte (PR1-CTL) Infusion
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myelogenous Leukemia focused on measuring Chronic Myelogenous Leukemia, CML, Allogeneic Hematopoietic Transplantation, Bone Marrow Transplant, PR1-Specific Cytotoxic T-Lymphocyte Infusion

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients with chronic myelogenous leukemia (CML) who have previously undergone allogeneic hematopoietic transplantation and have evidence of disease, as defined by a,b or c (a) >5% Philadelphia chromosome positive cells on cytogenetic studies >/= 3 months post-transplant
  2. (b) For patients in cytogenetic remission post-transplant, molecular evidence of disease at any time, defined as recurrence of quantitative PCR positivity for bcr-abl after achieving a molecular remission confirmed by 2 assays, 3 months apart or sooner if clinically indicated; OR a >10-fold increase in the relative expression of bcr-abl/abl detected and confirmed by a minimum of 2 consecutive PCR analysis, 3 months apart or sooner
  3. (c) Molecular evidence of persistent disease on Real time PCR (bcr-abl/ abl x 100 of 0.05 and not declining) >3 months post-transplantation after treatment with imatinib mesylate.
  4. Patients must have an HLA compatible related or unrelated donor capable of donating peripheral blood stem cells using apheresis techniques. This must be the same donor used for the original allogeneic hematopoetic transplantation. Patient must be HLA-A2 positive
  5. ECOG performance status < or = 2
  6. Serum bilirubin < or = 2 mg/dl
  7. Serum transaminases < 4 x normal
  8. Serum creatinine < or = 2 mg/dl
  9. No active uncontrolled infection
  10. HIV negative
  11. No acute and/or chronic GVHD requiring systemic steroid therapy
  12. Patient is not pregnant or breast feeding.
  13. Signed informed consent
  14. Patients must be off all immunosuppressive medications for at least 2 weeks prior to study entry.

Exclusion Criteria:

None.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    PR1-CTL

    Arm Description

    Two infusions of PR1-specific T lymphocytes (donor immune cells) 60 days apart. Starting infusion dose 1 x 106 nucleated cells/kg.

    Outcomes

    Primary Outcome Measures

    Maximally tolerated dose of donor PR1-specific cytotoxic T-lymphocytes (PR1-CTL)

    Secondary Outcome Measures

    Full Information

    First Posted
    March 18, 2009
    Last Updated
    March 3, 2014
    Sponsor
    M.D. Anderson Cancer Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00866346
    Brief Title
    PR1-Specific Cytotoxic T-Lymphocyte Infusion With Recurrent Chronic Myelogenous Leukemia (CML) After Allogeneic Hematopoietic Transplantation
    Official Title
    A Phase I Study of PR1-Specific Cytotoxic T-Lymphocyte Infusion for Patients With Recurrent CML After Allogeneic Hematopoietic Transplantation
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2014
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Study failed to accrue any patients due to regulatory issues with PR1 vaccine and T cell production.
    Study Start Date
    March 2008 (undefined)
    Primary Completion Date
    March 2015 (Anticipated)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    M.D. Anderson Cancer Center

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Primary Objective: To determine the maximally tolerated dose of donor PR1-specific cytotoxic T-lymphocytes (PR1-CTL) as treatment for relapsed or persistent chronic myelogenous leukemia (CML) after allogeneic hematopoietic transplantation from an HLA-matched related or unrelated donor. Secondary Objectives: To evaluate the immunological response following PR1-CTL treatment To evaluate the clinical efficacy by determining clinical, cytogenetic and molecular response rates within 6 months
    Detailed Description
    Before treatment starts, you will have a complete physical exam, including blood (about 2 tablespoons) tests. You will have a chest x-ray and bone marrow will be collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood pregnancy test. You will be treated with donor immune cells (T lymphocytes) that will specifically target certain leukemia cells in your body. Each participant will receive two doses of donor cells, 60 days apart. The second dose will be given 60 days after the first dose, at a higher dose level, as long as no serious side effects occur after the first dose and there is still disease present. Four dose levels of PR1-specific T lymphocytes will be considered. Up to 30 patients will be treated in cohorts of 3, starting at the lowest dose level, and not skipping an untried dose level when escalating. The trial will be stopped early if the lowest dose level is found to be unacceptably toxic. These cells will be given on an outpatient basis. After each donor cell infusions, you will be followed once a week in the outpatient clinic for at least 1 month and then every 3 months for at least one year. You will have routine blood (about 2 tablespoons) and urine tests at these visits. Participants experiencing side effects from their leukemia or leukemia treatment may need to be hospitalized earlier. You will also receive several other medications to help decrease the risk of infections while your immune system is weak. These include preventative antibiotics, antiviral drugs, and antifungal drugs. Bone marrow samples will be taken before the second cell infusion, and then 8 weeks, 12 weeks, 6 months and 1 year after the second cell infusion. This is an investigational study. A total of up to 30 patients will be take part in this study. All will be enrolled at UTMDACC.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Myelogenous Leukemia
    Keywords
    Chronic Myelogenous Leukemia, CML, Allogeneic Hematopoietic Transplantation, Bone Marrow Transplant, PR1-Specific Cytotoxic T-Lymphocyte Infusion

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    PR1-CTL
    Arm Type
    Experimental
    Arm Description
    Two infusions of PR1-specific T lymphocytes (donor immune cells) 60 days apart. Starting infusion dose 1 x 106 nucleated cells/kg.
    Intervention Type
    Biological
    Intervention Name(s)
    PR1-primed lymphocyte (PR1-CTL) Infusion
    Other Intervention Name(s)
    AHT, Allogenic Hemotopoietic Transplantation, PR1-CTL
    Intervention Description
    Two infusions of PR1-specific T lymphocytes (donor immune cells) 60 days apart. Starting infusion dose 1 x 106 nucleated cells/kg.
    Primary Outcome Measure Information:
    Title
    Maximally tolerated dose of donor PR1-specific cytotoxic T-lymphocytes (PR1-CTL)
    Time Frame
    Continuous reassessment, infusion day 0 and second infusion day 60+/- 7

    10. Eligibility

    Sex
    All
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients with chronic myelogenous leukemia (CML) who have previously undergone allogeneic hematopoietic transplantation and have evidence of disease, as defined by a,b or c (a) >5% Philadelphia chromosome positive cells on cytogenetic studies >/= 3 months post-transplant (b) For patients in cytogenetic remission post-transplant, molecular evidence of disease at any time, defined as recurrence of quantitative PCR positivity for bcr-abl after achieving a molecular remission confirmed by 2 assays, 3 months apart or sooner if clinically indicated; OR a >10-fold increase in the relative expression of bcr-abl/abl detected and confirmed by a minimum of 2 consecutive PCR analysis, 3 months apart or sooner (c) Molecular evidence of persistent disease on Real time PCR (bcr-abl/ abl x 100 of 0.05 and not declining) >3 months post-transplantation after treatment with imatinib mesylate. Patients must have an HLA compatible related or unrelated donor capable of donating peripheral blood stem cells using apheresis techniques. This must be the same donor used for the original allogeneic hematopoetic transplantation. Patient must be HLA-A2 positive ECOG performance status < or = 2 Serum bilirubin < or = 2 mg/dl Serum transaminases < 4 x normal Serum creatinine < or = 2 mg/dl No active uncontrolled infection HIV negative No acute and/or chronic GVHD requiring systemic steroid therapy Patient is not pregnant or breast feeding. Signed informed consent Patients must be off all immunosuppressive medications for at least 2 weeks prior to study entry. Exclusion Criteria: None.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Muzaffar H. Qazilbash, MD
    Organizational Affiliation
    UT MD Anderson Cancer Center
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Richard E. Champlin, MD, BS
    Organizational Affiliation
    UT MD Anderson Cancer Center
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Links:
    URL
    http://www.mdanderson.org
    Description
    UT MD Anderson Cancer Center website

    Learn more about this trial

    PR1-Specific Cytotoxic T-Lymphocyte Infusion With Recurrent Chronic Myelogenous Leukemia (CML) After Allogeneic Hematopoietic Transplantation

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