A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes
18 Years
70 Years
Both
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes
OBJECTIVES:
- 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.
- Determine the disease-free and overall survival of patients treated with this regimen.
- Determine the engraftment rate of donor cells in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Determine the extent and duration of acute and chronic graft-versus-host disease in
patients treated with this regimen.
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.
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study within 2.1 years.
Inclusion 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
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)
- FEV_1 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
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete response rate at day 100 after transplant
Safety Issue:
No
Principal Investigator
Selina M. Luger, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Abramson Cancer Center of the University of Pennsylvania
Authority:
United States: Federal Government
Study ID:
CDR0000256928
NCT ID:
NCT00045305
Start Date:
May 2005
Completion Date:
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- chronic myelomonocytic leukemia
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- refractory anemia
- refractory anemia with excess blasts
- refractory anemia with ringed sideroblasts
- secondary myelodysplastic syndromes
- atypical chronic myeloid leukemia, BCR-ABL1 negative
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- Neoplasms
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Mayo Clinic Scottsdale | Scottsdale, Arizona 85259 |
| Mayo Clinic - Jacksonville | Jacksonville, Florida 32224 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| Tufts-NEMC Cancer Center | Boston, Massachusetts 02111 |
| Jewish Hospital Cancer Center | Cincinnati, Ohio 45236 |
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
