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

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00045305

Purpose

RATIONALE: Photopheresis treats the patient's blood with drugs and ultraviolet light outside the body and kills the white blood cells. Giving photopheresis, pentostatin, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving pentostatin before transplant and cyclosporine or mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving pentostatin together with photopheresis and total-body irradiation work before donor bone marrow transplant in treating patients with myelodysplastic syndromes.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Drug: cyclosporine Drug: methotrexate Drug: methoxsalen Drug: mycophenolate mofetil Drug: pentostatin Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes

Resource links provided by NLM:

MedlinePlus related topics: Anemia Bone Marrow Transplantation Cancer Chronic Myeloid Leukemia Leukemia Myelodysplastic Syndromes

Drug Information available for: Methotrexate Pentostatin Cyclosporine Cyclosporin Mycophenolate mofetil hydrochloride Mycophenolate Mofetil Methoxsalen

U.S. FDA Resources

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

Primary Outcome Measures:

Complete response rate at day 100 after transplant [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease-free survival (DFS) 1-2 years after completion of study treatment [ Designated as safety issue: No ]
Overall survival (OS) 1-2 years after completion of study treatment [ Designated as safety issue: No ]
Engraftment of donor cells at days 30 and 100 [ Designated as safety issue: No ]
Toxicity or acute graft-versus-host disease at days 1-100 [ Designated as safety issue: Yes ]
Chronic graft-versus-host disease at 6 months, and then 1 and 2 years [ Designated as safety issue: No ]

Estimated Enrollment:	33
Study Start Date:	May 2005
Estimated Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045305

Locations

United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Massachusetts
Tufts-NEMC Cancer Center
Boston, Massachusetts, United States, 02111
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Ohio
Jewish Hospital Cancer Center
Cincinnati, Ohio, United States, 45236
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Selina M. Luger, MD

Abramson Cancer Center of the University of Pennsylvania

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Robert L. Comis, ECOG Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00045305 History of Changes
Other Study ID Numbers:	CDR0000256928, ECOG-E1902
Study First Received:	September 6, 2002
Last Updated:	April 10, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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-ABL negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable

Additional relevant MeSH terms:

Neoplasms
Leukemia
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cyclosporins
Cyclosporine
Methotrexate
Pentostatin
Mycophenolic Acid

Mycophenolate mofetil
Methoxsalen
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents

ClinicalTrials.gov processed this record on February 12, 2012