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

Primary Purpose

Accelerated Phase Chronic Myelogenous Leukemia, Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
therapeutic allogeneic lymphocytes
aldesleukin
laboratory biomarker analysis
flow cytometry
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Accelerated Phase Chronic Myelogenous Leukemia

Eligibility Criteria

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

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (adoptive immunotherapy)

Arm 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

In vivo persistence of transferred T-cells and assessment of migration to the bone marrow
Duration of response as assessed by PCR or cytogenetic analysis of peripheral blood and bone marrow samples
Proportion of responders

Full Information

First Posted
January 24, 2003
Last Updated
February 13, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00052598
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Study Start Date
September 2002 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Accelerated Phase Chronic Myelogenous Leukemia, Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Blastic Phase Chronic Myelogenous Leukemia, Childhood Chronic Myelogenous Leukemia, Childhood Myelodysplastic Syndromes, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (adoptive immunotherapy)
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Other Intervention Name(s)
ALLOLYMPH
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
aldesleukin
Other Intervention Name(s)
IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Toxicity rate associated with infusing donor CD8+CTL clones specific for PR3
Time Frame
From the first CTL infusion to 4 weeks after the final dose of CTL or IL-2
Secondary Outcome Measure Information:
Title
In vivo persistence of transferred T-cells and assessment of migration to the bone marrow
Time Frame
Baseline and days +7, +11, +14, +21, and +28 after each CTL infusion
Title
Duration of response as assessed by PCR or cytogenetic analysis of peripheral blood and bone marrow samples
Time Frame
Days +0, +15, +29, +50, +63, and at approximately 1 month after completion of all therapy
Title
Proportion of responders
Time Frame
Approximately one month after completion of all therapy

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gunnar Ragnarsson
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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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