Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

NCT00052520 | Completed Phase 1

• 3 other identifiers: 1655.00NCI-2009-01471P01CA018029
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial is studying the side effects of biological therapy and to see how well it works in treating patients with advanced myelodysplastic syndrome, chronic myeloid leukemia, acute myeloid leukemia, or acute lymphoblastic leukemia. Biological therapies, including immunotherapy, can potentially be used to stimulate the immune system and stop cancer cells from growing. Immunotherapy given to patients who have undergone donor stem cell transplantation may be a way to eradicate remaining cancer cells

Conditions

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; 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); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Toxicity rate associated with infusing donor CD8+ CTL clones specific for WT1 in patients at high risk for post transplant relapse of CML, AML, or ALL

  Assessed by Common Terminology Criteria (CTC) version 3.0.

  Up to 4 weeks after the final dose of CTL

Secondary Outcomes (1)

• Relapse of disease

  Up to 2 years

Study Arms (1)

Treatment

EXPERIMENTAL

See Detailed Description

Biological: therapeutic allogeneic lymphocytes; Biological: aldesleukin; Procedure: peripheral blood stem cell transplantation; Procedure: allogeneic bone marrow transplantation; Other: laboratory biomarker analysis; Genetic: gene expression analysis; Other: immunologic technique; Other: flow cytometry; Genetic: polymerase chain reaction; Genetic: cytogenetic analysis; Other: staining method

Interventions

therapeutic allogeneic lymphocytes BIOLOGICAL

Given IV

Also known as: ALLOLYMPH

Treatment

aldesleukin BIOLOGICAL

Given SC

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

Treatment

peripheral blood stem cell transplantation PROCEDURE

Undergo transplantation

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment

allogeneic bone marrow transplantation PROCEDURE

Undergo transplantation

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

Treatment

laboratory biomarker analysis OTHER

Correlative studies

Treatment

gene expression analysis GENETIC

Correlative studies

Treatment

immunologic technique OTHER

Correlative studies

Also known as: immunological laboratory methods, laboratory methods, immunological

Treatment

flow cytometry OTHER

Correlative studies

Treatment

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Treatment

cytogenetic analysis GENETIC

Correlative studies

Treatment

staining method OTHER

Correlative studies

Also known as: Staining

Treatment

Eligibility Criteria

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

You may qualify if:

• Eligibility for Enrollment:
• i) Pre-transplant: Patients undergoing allogeneic hematopoietic stem cell transplantation for refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-t), CML beyond chronic phase, AML beyond first remission, Philadelphia chromosome (BCR-ABL)-positive ALL at any stage, any ALL beyond first remission, primary refractory AML or ALL, 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);
• ii) Post-transplant: Patients who have relapsed after transplant (morphologic, flow cytometric, cytogenetic and molecular relapse) can be offered enrollment on the protocol and may undergo therapy if it is considered possible to control their disease while waiting for the generation of study therapy
• b. Patients and donors must both express an human leukocyte antigen (HLA)-allele for which it is possible to generate WT1-specific clones for
• c. 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 WT1 must have been generated and have completed Quality Control (QC) testing
• a. Patients must have had \> 5% morphologic blasts detectable in bone marrow or peripheral blood just prior to or at the time of transplant
• b. Patients must have evidence of post transplant recovery of normal hematopoiesis (absolute neutrophil count \[ANC\] \> 500/mm\^3) for at least 7 days prior to the initiation of CTL infusions
• c. 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 WT1 must have been generated and have completed Quality Control (QC) testing
• a. Patients must have evidence of recurrent disease post transplant; this includes patients with the following:
• i) 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
• ii) 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
• iii) Cytogenetic relapse 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
• iv) Molecular relapse defined as: one or more positive polymerase chain reaction (PCR) assays for the presence of clonotypic immunoglobulin heavy chain (IgH) or T cell receptor (TCR) gene rearrangement in patients transplanted for B-or T-cell acute lymphoblastic leukemia, respectively; one or more positive post transplant reverse transcription (RT)-PCR assays for the presence of BCR-ABL messenger ribonucleic acid (mRNA) fusion transcripts in patients transplanted for Philadelphia chromosome (BCRABL)-positive acute lymphoblastic leukemia; (for CML) a PCR assay of bone marrow (BM) or peripheral blood mononuclear cell (PBMC) positive for the presence of the BCR/ABL 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 WT1 have not been generated in time for planned infusion (these patients can potentially be treated later if CTL become available); Also we will exclude patients whose malignant cells do not over express WT-1, 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
• DONOR: Medical conditions precluding either leukapheresis or blood donation may include but are not limited to:
• Inadequate age or weight (leukapheresis donors must be age 18 or older, other criteria per physician discretion)
• Active infection, with or without antibiotic treatment
• Recent hepatitis exposure, hepatitis A or B antigenemia, or hepatitis C antibody positivity
• Pregnancy or nursing; HIV or human T-lymphotropic virus (HTLV) infection
• Severe cardiovascular disease (e.g., uncontrolled hypertension, recent myocardial infarction \[MI\], or unstable angina)

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

Congenital Abnormalities; Leukemia, Myelomonocytic, Chronic; Thrombocythemia, Essential; Polycythemia Vera; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts

Interventions

aldesleukin; Interleukin-2; Peripheral Blood Stem Cell Transplantation; Transplantation; Gene Expression Profiling; Immunologic Techniques; Flow Cytometry; Polymerase Chain Reaction; Cytogenetic Analysis; Coloring Agents; Staining and Labeling

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Myeloproliferative Disorders; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Surgical Procedures, Operative; Genetic Techniques; Investigative Techniques; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Nucleic Acid Amplification Techniques; Specialty Uses of Chemicals; Chemical Actions and Uses; Histocytological Preparation Techniques; Histological Techniques

Study Officials

• Merav Bar

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 24, 2003
• First Posted: January 27, 2003
• Study Start: September 1, 2002
• Primary Completion: April 1, 2011
• Study Completion: June 1, 2013
• Last Updated: March 29, 2017

Record last verified: 2013-07

Locations

US (1)