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Donor Stem Cell Transplantation in Treating Patients With Myelodysplastic Syndrome and Myeloproliferative Disorders
This study is ongoing, but not recruiting participants.
First Received: January 24, 2003   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00052546
  Purpose

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Mycophenolate mofetil, cyclosporine, and donor white blood cells may prevent this rejection.

PURPOSE: Phase I/II trial to study the effectiveness of donor stem cell transplantation in treating patients who have myelodysplastic syndrome or myeloproliferative disorder.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: therapeutic allogeneic lymphocytes
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For The Treatment Of Myelodysplatic Syndromes And Myeloproliferative Disorders (Except CML): A Multi-Center Trial

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: September 2002
Detailed Description:

OBJECTIVES:

  • Determine the efficacy of non-myeloablative allogeneic hematopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndromes or myeloproliferative disorders.
  • Determine the safety profile of this regimen, in terms of incidence of graft-vs-host disease, graft rejection, and non-relapse mortality, in these patients.
  • Determine the efficacy of a strategy for donor lymphocyte infusion based primarily on defined criteria of persistent or progressive disease in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to donor status (related vs unrelated).

  • Conditioning:Patients receive fludarabine IV over 30 minutes once daily on days -4 to -2. Patients undergo total body irradiation on day 0.
  • Immunosuppression:

    • Related Donor:Patients receive oral cyclosporine twice daily beginning on day -3 followed by a taper beginning on day 56 and continuing until day 81 or day 177 in the absence of graft-vs-host disease (GVHD). Patients also receive oral mycophenolate mofetil twice daily on days 0-27.
    • Unrelated Donor:Patients receive oral cyclosporine twice daily beginning on day -3 followed by a taper beginning on day 100 and continuing until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil three times daily beginning on day 0 followed by a taper beginning on day 40 and continuing until day 96.
  • Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT): Patients undergo AHSCT transplantation on day 0.
  • Donor lymphocyte infusion (DLI): Eligible patients (at least mixed hematopoietic chimerism, no GVHD, and persistent or progressive disease) may receive DLI IV over 30 minutes beginning 1-2 weeks after immunosuppression. Patients may receive up to 3 infusions.

Patients are followed at months 3, 4, 6, 9, 12, 18, and 24 and then annually thereafter.

PROJECTED ACCRUAL: A total of 200 patients (100 per stratum) will be accrued for this study within 3 years.

  Eligibility

Ages Eligible for Study:   up to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Myelodysplastic syndromes (MDS)

    • Diagnosis of MDS classifiable by the FAB system as any of the following:

      • Refractory anemia (RA)
      • RA with ringed sideroblasts
      • RA with excess blasts (RAEB)
      • RAEB in transformation
      • Chronic myelomonocytic leukemia
      • MDS transformed to acute leukemia
    • Patients with advanced MDS must be cytoreduced to less than 10% marrow blasts within past 21 days
    • High-risk disease by the International Prognostic Scoring System (IPSS) score (e.g., "intermediate-2" or "high risk")

      • Lower-risk disease by the IPSS score (e.g., "intermediate-1" or "low risk") allowed if evidence of progression is present (e.g., an increasing transfusion requirement)
  • Myeloproliferative disorders

    • Diagnosis of any of the following:

      • Atypical chronic myelogenous leukemia and Philadelphia chromosome-negative

        • Chronic phase
        • Excess blasts or blastic transformation
      • Polycythemia vera with persistent thrombotic or hemorrhagic complications despite conventional therapy OR progressed to post-polycythemic marrow fibrosis
      • Essential thrombocythemia with persistent thrombotic or hemorrhagic complications despite conventional therapy OR progressed to myelofibrosis
      • Agnogenic myeloid metaplasia with 1 of the following criteria:

        • High-risk disease according to the Lille scoring system (e.g., "intermediate" or "high risk")
        • Lower-risk disease according to the Lille scoring system (e.g., "low risk") with abnormal cytogenetics
  • Ineligible for a curative autologous transplantation
  • No active CNS involvement
  • Related donor

    • Genotypically or phenotypically HLA-identical
    • ABO incompatibility acceptable
    • No identical twin OR
  • Unrelated donor

    • HLA-matched for HLA-DRB1 and DQB1
    • Serologic match for all recognized HLA-A, HLA-B, and HLA-C antigens
    • Molecular match for at least 5 of 6 HLA-A, HLA-B, or HLA-C antigens
    • ABO incompatibility acceptable
    • No bone marrow donors

PATIENT CHARACTERISTICS:

Age

  • 50 to 74 OR
  • Under 50 and at high risk for regimen-related toxicity using standard high-dose regimens

    • High-risk factors include pre-existing conditions such as chronic lung, kidney, liver, or heart disease

Performance status

  • Karnofsky 70-100%

Life expectancy

  • Not specified

Hematopoietic

  • See DIsease Characteristics

Hepatic

  • See Age
  • Bilirubin no greater than 2 times upper limit of normal (ULN)
  • AST or ALT no greater than 4 times ULN

Renal

  • See Age

Cardiovascular

  • See Age
  • Ejection fraction at least 40%
  • No symptomatic congestive heart failure requiring therapy
  • No poorly controlled cardiac arrhythmias
  • No poorly controlled hypertension with inability to maintain a steady blood pressure of 150/90

Pulmonary

  • See Age
  • No requirement for supplemental oxygen
  • DLCO at least 50% of predicted
  • Total lung capacity at least 30%
  • FEV_1 at least 30%

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 1 year after study completion
  • HIV negative
  • No severe psychological illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent hematopoietic growth factors during mycophenolate mofetil administration

Chemotherapy

  • At least 21 days since prior chemotherapy and recovered

    • Hydroxyurea or anagrilide to manage elevated cell counts allowed up until beginning of study therapy

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00052546

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
United States, Colorado
University of Colorado Cancer Center at University of Colorado Health Sciences Center
Denver, Colorado, United States, 80010
United States, Oregon
Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84132
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Germany
Universitaet Leipzig
Leipzig, Germany, D-04103
Italy
University of Torino
Torino, Italy, 10126
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Study Chair: Brenda Sandmaier, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000258519, FHCRC-1732.00
Study First Received: January 24, 2003
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00052546     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory anemia
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
chronic phase chronic myelogenous leukemia
Philadelphia chromosome negative chronic myelogenous leukemia
polycythemia vera
essential thrombocythemia
chronic idiopathic myelofibrosis
blastic phase chronic myelogenous leukemia
chronic eosinophilic leukemia
chronic neutrophilic leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
childhood myelodysplastic syndromes

Study placed in the following topic categories:
Antimetabolites
Polycythemia
Philadelphia Chromosome
Chronic Myelomonocytic Leukemia
Blast Crisis
Cyclosporine
Immunologic Factors
Precancerous Conditions
Leukemia, Myeloid, Chronic-Phase
Cyclosporins
Refractory Anemia
Leukemia
Preleukemia
Anemia, Refractory
Antifungal Agents
Chronic Myeloproliferative Disorders
Mycophenolate mofetil
Neoplasm Metastasis
Thrombocytosis
Hemorrhagic Thrombocythemia
Thrombocythemia, Hemorrhagic
Myelodysplastic Myeloproliferative Disease
Polycythemia Vera
Myelofibrosis
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myeloproliferative Disorders
Anemia

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Cyclosporine
Precancerous Conditions
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclosporins
Leukemia
Preleukemia
Pathologic Processes
Therapeutic Uses
Syndrome
Antifungal Agents
Mycophenolate mofetil
Dermatologic Agents
Neoplasms by Histologic Type
Disease
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Enzyme Inhibitors
Fludarabine monophosphate
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Fludarabine
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 02, 2009