Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Donor Stem Cell Transplantation in Treating Patients With Myelodysplastic Syndrome and Myeloproliferative Disorders

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed Under 75 NCI FHCRC-1732.00 NCT00052546

Objectives

1. Determine the efficacy of non-myeloablative allogeneic hematopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndromes or myeloproliferative disorders.
2. 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.
3. Determine the efficacy of a strategy for donor lymphocyte infusion based primarily on defined criteria of persistent or progressive disease in these patients.

Entry 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

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

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%
• FEV₁ 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

Brenda Sandmaier, MD, Protocol chair		Ph: 206-288-1024

Registry Information
Official Title		Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For The Treatment Of Myelodysplatic Syndromes And Myeloproliferative Disorders (Except CML): A Multi-Center Trial
Trial Start Date		2002-09-11
Registered in ClinicalTrials.gov		NCT00052546
Date Submitted to PDQ		2002-10-09
Information Last Verified		2004-04-08
NCI Grant/Contract Number		P30-CA15704, N01-HL36444

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