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Donor Peripheral Stem Cell Transplant and Donor Natural Killer Cell Transplant After Total-Body Irradiation, Thiotepa, Fludarabine, and Muromonab-CD3 in Treating Patients With Leukemia or Other Blood Diseases

This study has been terminated.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Ann Woolfrey, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00450983
First received: March 20, 2007
Last updated: April 17, 2017
Last verified: April 2017
  Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell and donor natural killer cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving a donor peripheral stem cell transplant and a donor natural killer cell transplant after total-body irradiation, thiotepa, fludarabine, and muromonab-CD3 works in treating patients with leukemia or other blood diseases.


Condition Intervention Phase
Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Biological: muromonab-CD3 Biological: natural killer cell therapy Drug: fludarabine phosphate Drug: methotrexate Drug: thiotepa Genetic: gene expression analysis Other: flow cytometry Other: immunologic technique Procedure: allogeneic hematopoietic stem cell transplantation Procedure: in vitro-treated peripheral blood stem cell transplantation Radiation: total-body irradiation Phase 2

Study Type: Interventional
Study Design: Masking: No masking
Primary Purpose: Treatment
Official Title: Transplantation of Haploidentical CD34+ Purified Peripheral Blood Stem Cells With NK-Cell Add-Back Following Conditioning With Total Body Irradiation, Thiotepa, Fludarabine and OKT3

Resource links provided by NLM:


Further study details as provided by Ann Woolfrey, Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD) [ Time Frame: Up to day 100 ]
    Count of participants with acute GVHD grades III-IV.


Secondary Outcome Measures:
  • Risk for Mortality From Infection Before Day 180 [ Time Frame: Up to day 180 ]
    Count of participant deaths from infection up to day 180.

  • Risk for Graft Failure [ Time Frame: Engraftment documented day +20 ]
    Count of participant that had graft failure.

  • Risk for Life-threatening Infections [ Time Frame: Up to day 100 ]
    Count of participants with life-threatening infections

  • Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft [ Time Frame: Up to 5 years ]
  • Cytomegalovirus-specific T Cells in Product and Donor Graft [ Time Frame: Up to 5 years ]
  • Genotype and Phenotype of Donor Killer Cell Immunoglobulin-like Receptor Expression According to Time After Hematopoietic Stem Cell Transplantation (HSCT) [ Time Frame: Up to 5 years ]
  • Reconstitution of NK Function According to Time After HSCT [ Time Frame: Up to 5 years ]
  • Expression of NKG2 Ligands of Leukemic Blasts [ Time Frame: Up to 5 years ]

Enrollment: 1
Study Start Date: December 2006
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the effect of haploidentical donor CD34+ purified peripheral blood stem cells and donor natural killer (NK) cells on the risk of developing grades III-IV acute graft-vs-host disease in patients with leukemia or other hematologic diseases.

Secondary

  • Determine the risk for mortality from infection before day 180 in patients treated with this regimen.
  • Determine the risk for graft rejection in patients treated with this regimen.
  • Determine the risk for life-threatening infections in patients treated with this regimen.
  • Determine the concentration of subsets of NK, NK-T, T cells, and dendritic cells in the CD34+ NK/NK-T-enriched graft.
  • Determine cytomegalovirus-specific T-cells in product and donor graft.
  • Determine the genotype and phenotype of donor killer cell immunoglobulin-like receptor expression according to time after hematopoietic stem cell transplantation (HSCT).
  • Determine the reconstitution of NK function according to time after HSCT.
  • Determine the expression of NKG2 ligands of leukemic blasts.

OUTLINE: Patients are stratified according to age (≤ 7 years vs > 7 years).

  • Conditioning regimen: Patients 7 years of age or younger undergo total-body irradiation (TBI) twice daily on days -11 to -9. Patients over 7 years of age undergo TBI once on day -9. All patients receive thiotepa IV over 2 hours on days -8 and -7, fludarabine phosphate IV on days -6 to -3 and muromonab-CD3 on days -6 to 6. Patients with acute lymphoblastic leukemia or leukemia in the spinal fluid also receive methotrexate intrathecally prior to and after donor peripheral blood stem cell (PBSC) transplantation .
  • Donor PBSC transplantation: Patients undergo donor PBSC transplantation comprising CD34+ purified PBSCs and natural killer (NK) cells on day 0.

Blood samples are collected in weeks 1-4, 6, 8, and 12. Analysis of samples includes quantitation of NK, NK-T, and T-cell subsets (CD3, CD4, and CD8) by flow cytometry; donor killer cell immunoglobulin-like receptor genotype and phenotype; interferon-gamma levels; and NK cytotoxicity. Samples are also analyzed by leukemic blast assay to determine if ligands that activate NK cells are expressed.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following life-threatening hematological malignancies:

    • Acute lymphoblastic leukemia meeting 1 of the following criteria:

      • Advanced beyond first remission
      • In first remission with high-risk prognostic features, including any of the following:

        • Philadelphia chromosome-positive disease
        • Chromosome 11q23 abnormality
        • Hypodiploid
        • Failed to achieve first remission within 1 month after induction
    • Acute myeloid leukemia (AML) meeting 1 of the following criteria:

      • Advanced beyond first remission
      • First remission with high-risk prognostic features, including any of the following:

        • Chromosome 11q23 abnormality
        • Chromosome del 7q
        • Secondary AML
        • Failed to achieve first remission within 1 month after induction
    • Myelodysplastic syndromes with International Prognostic Score > 1
    • Chronic myelogenous leukemia in accelerated or blastic phase
  • No active CNS disease
  • No suitable HLA-matched related or unrelated donor available
  • Haploidentical family member available as donor of partially HLA-matched peripheral blood stem cells

    • Least degree of mismatch to HLA-A, B, C, DRB1, and DQB1
    • No mismatch for a single HLA-A, B, C, DRB1, or DQB1 antigen
    • Donor killer cell immunoglobulin-like receptor ligand group expression preferably different than patient

PATIENT CHARACTERISTICS:

  • LVEF ≥ 45%
  • DLCO ≥ 60% of predicted
  • AST and ALT ≤ 2 times upper limit of normal (ULN) (unless due to malignancy)
  • Bilirubin ≤ 2 times ULN (unless due to malignancy)
  • No life expectancy < 6 months due to coexisting disease other than the malignancy
  • No active infection (e.g., polymerase chain reaction [PCR] evidence for cytomegalovirus, human herpes virus 6, or invasive fungal infection)
  • No prior infections without evidence of resolution by PCR or imaging studies within the past 2 months
  • No hypersensitivity to murine antibodies
  • No known HIV positivity
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior marrow transplantation with total body irradiation > 400 cGy
  • No concurrent therapies for seizure disorder
  • No growth factors for 21 days after transplantation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00450983

Locations
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Ann Woolfrey, MD Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: Ann Woolfrey, Principal Investigator, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00450983     History of Changes
Other Study ID Numbers: 1965.00
R01AI053193 ( U.S. NIH Grant/Contract )
P30CA015704 ( U.S. NIH Grant/Contract )
FHCRC-1965.00
CDR0000533834 ( Registry Identifier: PDQ )
Study First Received: March 20, 2007
Results First Received: April 17, 2017
Last Updated: April 17, 2017

Keywords provided by Ann Woolfrey, Fred Hutchinson Cancer Research Center:
graft versus host disease
adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
childhood acute lymphoblastic leukemia in remission
recurrent childhood acute lymphoblastic leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
childhood acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
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)
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Graft vs Host Disease
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Immune System Diseases
Methotrexate
Fludarabine phosphate
Thiotepa
Muromonab-CD3
Vidarabine
Fludarabine
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on July 21, 2017