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

Alternate Title

Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Temporarily closed	18 to 70	NCI	ECOG-E1902 NCT00045305, E1902

Objectives

1. Determine the complete response rate in patients with myelodysplastic syndromes treated with reduced-intensity allogeneic bone marrow transplantation, including photopheresis, total body irradiation, and pentostatin.
2. Determine the disease-free and overall survival of patients treated with this regimen.
3. Determine the engraftment rate of donor cells in patients treated with this regimen.
4. Determine the toxicity of this regimen in these patients.
5. Determine the extent and duration of acute and chronic graft-versus-host disease in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• One of the following cytologically proven myelodysplastic syndromes
  • Refractory anemia (RA)
  • RA with ringed sideroblasts
  • RA with excess blasts
  • Chronic myelomonocytic leukemia
• International Prognosis Scoring System (IPSS) score of at least 0.5 OR red cell transfusion dependence for at least 6 months (2 units per month)
  • Patients with an IPSS score less than 0.5 may be eligible provided they previously had a higher IPSS score and received chemotherapy at that time
• Suitable HLA-matched donor (related or unrelated) available
  • No cord blood donors
  • Related donors must be genotypically matched (HLA A, B and DR) at 5/6 or 6/6 loci and may be a sibling, parent, or child
  • Unrelated donors must have high resolution typing done at A, B, C and DR, and must be matched at all or may have a single antigen or allele mismatch at no more than one of these loci
• Patients must have < 20% blasts on bone marrow study within 1 month of study entry

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• See Hematopoietic
• At least 90 days since prior autologous bone marrow transplantation
• No prior myeloablative or nonmyeloablative allogeneic transplantation for myelodysplastic syndrome or acute myeloid leukemia

Chemotherapy

• Recovered from prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age

• 18 to 70

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• See Disease Characteristics
• Serum erythropoietin level greater than 100 for patients who have not received a prior course of epoetin alfa
• No iron deficiency
  • Iron deficiency anemia treated with iron replacement therapy allowed

Hepatic

• Bilirubin less than 2.0 mg/dL
• Alkaline phosphatase less than 2 times upper limit of normal (ULN)
• AST and ALT less than 3 times ULN

Renal

• Creatinine less than 2.0 mg/dL

  OR

• Creatinine clearance greater than 50 mL/min

Cardiovascular

• LVEF at least 45% by MUGA or echocardiogram

Pulmonary

• DLCO at least 50% of predicted (corrected for hemoglobin)
• FEV₁ at least 50% of predicted

Other

• Physically and psychologically capable of undergoing study regimen
• Able to receive 600 cGy of total body irradiation
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• No other medical condition that would reduce life expectancy
• No active ongoing infection

Expected Enrollment

A total of 33 patients will be accrued for this study within 2.1 years.

Outcomes

Complete response rate at day 100 after transplant

Disease-free survival (DFS) 1-2 years after completion of study treatment
Overall survival (OS) 1-2 years after completion of study treatment
Engraftment of donor cells at days 30 and 100
Toxicity or acute graft-versus-host disease at days 1-100
Chronic graft-versus-host disease at 6 months, and then 1 and 2 years

Outline

This is a multicenter study.

• Preparative Regimen: Patients undergo photopheresis using methoxsalen on days -7 and -6 and receive pentostatin IV continuously on days -5 and -4. Total body irradiation is administered on days -3 and -2 for a total of 3 doses.
• Transplantation: Allogeneic bone marrow or peripheral blood stem cells are infused on day 0.
• Acute graft-vs-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV on days -1 to 30 and then orally every 12 hours. Cyclosporine dose is then tapered beginning after day 50 and continuing for 6 months in the absence of GVHD. Once cyclosporine dose is significantly decreased, oral mycophenolate mofetil (MMF) is then administered twice a day. MMF dose is then tapered for 12 months in the absence of GVHD. Patients also receive methotrexate IV on days 1 and 3.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Selina Luger, MD, Protocol chair		Ph: 215-662-6348

Registry Information
Official Title		A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes
Trial Start Date		2005-05-31
Trial Completion Date		2008-02-15 (estimated)
Registered in ClinicalTrials.gov		NCT00045305
Date Submitted to PDQ		2002-06-14
Information Last Verified		2009-09-24
NCI Grant/Contract Number		CA21115

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