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

NCT00052598 | Terminated Phase 1

• 3 other identifiers: 1671.00NCI-2010-00826P01CA018029
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

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

  From the first CTL infusion to 4 weeks after the final dose of CTL or IL-2

Secondary Outcomes (3)

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

  Baseline and days +7, +11, +14, +21, and +28 after each CTL infusion

• Duration of response as assessed by PCR or cytogenetic analysis of peripheral blood and bone marrow samples

  Days +0, +15, +29, +50, +63, and at approximately 1 month after completion of all therapy

• Proportion of responders

  Approximately one month after completion of all therapy

Study Arms (1)

Treatment (adoptive immunotherapy)

EXPERIMENTAL

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.

Biological: therapeutic allogeneic lymphocytes; Biological: aldesleukin; Other: laboratory biomarker analysis; Other: flow cytometry

Interventions

therapeutic allogeneic lymphocytes BIOLOGICAL

Given IV

Also known as: ALLOLYMPH

Treatment (adoptive immunotherapy)

aldesleukin BIOLOGICAL

Given SC

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

Treatment (adoptive immunotherapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (adoptive immunotherapy)

flow cytometry OTHER

Correlative studies

Treatment (adoptive immunotherapy)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Congenital Abnormalities; Blast Crisis; Leukemia, Myeloid, Acute

Interventions

aldesleukin; Interleukin-2; Flow Cytometry

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Gunnar Ragnarsson

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2003
• First Posted: January 27, 2003
• Study Start: September 1, 2002
• Primary Completion: November 1, 2009
• Study Completion: June 1, 2011
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

US (1)