Therapeutic Allogeneic Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

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Brief Title

Therapeutic Allogeneic Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

Official Title

Phase I/II Study of Adoptive Immunotherapy With CD8+ Proteinase 3 (Myeloblastin)-Specific CTL Clones for HLA-A2+ Patients With Relapse or Progression of Disease After Allogeneic Hematopoietic Stem Cell Transplant for High Risk Myeloid Leukemias

Brief Summary

      This phase I/II trial is studies the side effects of giving therapeutic allogeneic
      lymphocytes together with aldesleukin and to see how well it works in treating patients with
      high-risk or recurrent myeloid leukemia after undergoing donor stem cell transplant.
      Biological therapies, such as therapeutic autologous lymphocytes, may stimulate the immune
      system in different ways and stop cancer cells from growing. Aldesleukin may stimulate the
      white blood cells to kill cancer cells. Giving therapeutic autologous lymphocytes together
      with aldesleukin may kill more cancer cells
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and potential toxicities associated with infusing donor CD8+
      cytotoxic T lymphocytes (CTL) clones specific for Proteinase 3 (Myeloblastin) in patients
      with relapse/progression of high risk myeloid leukemias after transplant.

      SECONDARY OBJECTIVES:

      I. To determine the in vivo persistence of transferred T cells and assess migration to the
      bone marrow, a predominant site of leukemic relapse.

      II. To determine if adoptively transferred proteinase 3 (PR3)-specific T cells mediate
      antileukemic activity.

      OUTLINE:

      Patients receive allogeneic CD8+ PR3-specific CTLs intravenously (IV) over 1-2 hours on days
      0, 7, 14, 28, and 49 and aldesleukin subcutaneously (SC) twice daily on days 28-41 and 49-63
      in the absence of unacceptable toxicity.

      After completion of study treatment, patients are followed up every 1-3 months.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Toxicity rate associated with infusing donor CD8+CTL clones specific for PR3

Secondary Outcome

 In vivo persistence of transferred T-cells and assessment of migration to the bone marrow

Condition

Accelerated Phase Chronic Myelogenous Leukemia

Intervention

therapeutic allogeneic lymphocytes

Study Arms / Comparison Groups

 Treatment (adoptive immunotherapy)
Description:  Patients receive allogeneic CD8+ PR3-specific CTLs IV over 1-2 hours on days 0, 7, 14, 28, and 49 and aldesleukin SC twice daily on days 28-41 and 49-63 in the absence of unacceptable toxicity.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

7

Start Date

September 2002

Completion Date

June 2011

Primary Completion Date

November 2009

Eligibility Criteria

        Inclusion Criteria:

          -  Patients undergoing allogeneic hematopoietic stem cell transplantation for chronic
             myelogenous leukemia (CML) in accelerated or blast phase, acute myeloid leukemia (AML)
             beyond first remission, primary refractory AML, therapy-related AML at any stage, or
             acute leukemia at any stage arising in a patient with an antecedent diagnosis of a
             myelodysplastic or myeloproliferative syndrome (including chronic myelomonocytic
             leukemia, CML, polycythemia vera, essential thrombocytosis, and agnogenic myeloid
             metaplasia with myelofibrosis)

          -  Patients and donors must both be human leukocyte antigen (HLA)-A2 positive

          -  Patients must be able to provide blood and bone marrow samples required for this
             protocol

          -  Eligibility for Prophylactic Treatment with CD8+ CTL After Transplant (Highest Risk
             Subgroup):

          -  At time of planned treatment, CD8+ CTL specific for PR3 must have been generated and
             have completed Quality Control (QC) testing

          -  Patients must have had > 5% morphologic blasts detectable in bone marrow or peripheral
             blood just prior to or at the time of transplant

          -  Patients must have evidence of posttransplant recovery of normal hematopoiesis
             (absolute neutrophil count [ANC] > 500/mm^3) for at least 7 days prior to the
             initiation of CTL infusions

          -  Patients on immunosuppressive therapy for graft-versus-host disease (GVHD) are
             eligible for treatment if not receiving corticosteroids or if the dose of
             corticosteroids can be tapered to < the equivalent of 0.5 mg/kg/day of prednisone; The
             patient's symptoms have to remain stable and unlikely to increase to stage III or IV
             acute GVHD or chronic GVHD is unlikely to progress following the change in
             immunosuppressive therapy, after an appropriate monitoring period, as deemed by the
             patients treating physician and the principal investigator

          -  Eligibility for Treatment with CD8+ CTL at the Time of Relapse After Transplant (All
             Others):

          -  At time of planned treatment, CD8+ CTL specific for PR3 must have been generated and
             have completed Quality Control (QC) testing

          -  Patients must have evidence of recurrent/progressive disease posttransplant

          -  Morphologic relapse defined as one or more of the following: abnormal peripheral
             blasts in absence of growth factor therapy, abnormal bone marrow blasts > 5% of
             nucleated cells, extramedullary chloroma or granulocytic sarcoma

          -  Flow cytometric relapse defined as the appearance in the peripheral blood or bone
             marrow of cells with an abnormal immunophenotype detected by flow cytometry that is
             consistent with leukemia recurrence/progression

          -  Cytogenetic relapse/progression defined as the appearance in one or more metaphases
             from bone marrow or peripheral blood cells of either a non-constitutional cytogenetic
             abnormality identified in at least one cytogenetic study performed prior to transplant
             or a new abnormality known to be associated with leukemia; (for CML), an increase in
             the number of Ph+ metaphases from bone marrow or peripheral blood between two
             consecutive samples after engraftment, or an increase in the percentage of BCR/ABL+
             cells by fluorescence in situ hybridization (FISH) between two consecutive samples
             after engraftment

          -  Molecular relapse/progression defined as a polymerase chain reaction (PCR) assay of
             bone marrow (BM) or peripheral blood mononuclear cells (PBMC) positive for the
             presence of the BCR/ABL messenger ribonucleic acid (mRNA) fusion transcript that
             quantitatively increases by greater than one order of magnitude on a subsequent sample

          -  Patients on immunosuppressive therapy for GVHD at the time of relapse are eligible for
             treatment if not receiving corticosteroids or if the dose of corticosteroids can be
             tapered to < the equivalent of 0.5 mg/kg/day of prednisone; the patient's symptoms
             have to remain stable and unlikely to increase to stage III or IV acute GVHD or
             chronic GVHD is unlikely to progress following the change in immunosuppressive
             therapy, after an appropriate monitoring period, as deemed by the patient's treating
             physician and the principal investigator

        Exclusion Criteria:

          -  Exclusions for Treatment at the Time of Relapse/Progression After Transplant:

          -  Patients for whom CD8+ CTL clones specific for PR3 have not been generated by the time
             of disease relapse/progression post-transplant; these patients can potentially be
             treated later if CTL become available; patients whose malignant cells do not
             overexpress PR3, based on direct analysis of a bone marrow sample with > 50% blasts or
             of leukemia cells isolated for expression analysis; in either case, patients will be
             informed about the availability of other treatment protocols for which they might be
             eligible

          -  Patients with Karnofsky performance status or Lansky play score =< 30%

          -  Patients with current stage III or IV GVHD unresponsive to therapy or requiring
             therapy with anti-CD3 mAb, prednisone > 0.5 mg/kg/day (or corticosteroid equivalent),
             or other treatments resulting in the ablation or inactivation of T cells (such as
             other anti-T cell monoclonal antibodies); although the concurrent use of cyclosporine,
             FK506, or mycophenolate mofetil (MMF) is not strictly an exclusion criterion, attempts
             should be made to discontinue it if possible

          -  Patients requiring concurrent therapy with hydroxyurea or other agents that may
             interfere with the function or survival of infused CTL clones

          -  Patients with a preexisting nonhematopoietic organ toxicity that is deemed by the
             principal investigator to place the patient at unacceptable risk for treatment on the
             protocol

          -  Patients with graft rejection or failure
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Gunnar Ragnarsson, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00052598

Organization ID

1671.00

Secondary IDs

NCI-2010-00826

Responsible Party

Sponsor

Study Sponsor

Fred Hutchinson Cancer Research Center

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Gunnar Ragnarsson, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


Verification Date

February 2017