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

Sponsors and Collaborators:	Eastern Cooperative Oncology Group 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 Diseases	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:	Treatment, Open Label
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 Leukemia, Adult Acute Leukemia, Adult Chronic Radiation Therapy

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	Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, Florida
Mayo Clinic - Jacksonville	Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, Massachusetts
Tufts-NEMC Cancer Center	Recruiting
Boston, Massachusetts, United States, 02111
Contact: Kellie A. Sprague 617-636-6100
United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, Ohio
Case Comprehensive Cancer Center	Recruiting
Cleveland, Ohio, United States, 44106-5065
Contact: Clinical Trials Office - Case Comprehensive Cancer Center 800-641-2422
Jewish Hospital Cancer Center	Recruiting
Cincinnati, Ohio, United States, 45236
Contact: E. Randolph Broun, MD 513-686-5482
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104-4283
Contact: Clinical Trials Office - Abramson Cancer Center of the Univers 800-474-9892
United States, South Dakota
Avera Cancer Institute	Recruiting
Sioux Falls, South Dakota, United States, 57105
Contact: Loren K. Tschetter, MD 605-328-8000
Medical X-Ray Center, PC	Recruiting
Sioux Falls, South Dakota, United States, 57105
Contact: Loren K. Tschetter, MD 605-328-8000
Sanford Cancer Center at Sanford USD Medical Center	Recruiting
Sioux Falls, South Dakota, United States, 57117-5039
Contact: Clinical Trials Office - Sanford Cancer Center 605-328-1367

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Selina M. Luger, MD

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:	ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers:	CDR0000256928, ECOG-E1902
Study First Received:	September 6, 2002
Last Updated:	May 2, 2009
ClinicalTrials.gov Identifier:	NCT00045305 History of Changes
Health Authority:	Unspecified

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
myelodysplastic/myeloproliferative disease, unclassifiable

Study placed in the following topic categories:

Antimetabolites
Chronic Myelomonocytic Leukemia
Pentostatin
Cyclosporine
Immunologic Factors
Precancerous Conditions
Folate
Cyclosporins
Vitamin B9
Refractory Anemia
Leukemia
Preleukemia
Anemia, Refractory
Methoxsalen
Antifungal Agents

Neoplasm Metastasis
Mycophenolate mofetil
Methotrexate
Myelodysplastic Myeloproliferative Disease
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myeloproliferative Disorders
Anemia
Leukemia, Myeloid
Folinic Acid
Folic Acid Antagonists
Immunosuppressive Agents
Folic Acid

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Pentostatin
Antimetabolites, Antineoplastic
Cyclosporine
Precancerous Conditions
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Cyclosporins
Leukemia
Preleukemia
Pathologic Processes

Methoxsalen
Therapeutic Uses
Antifungal Agents
Syndrome
Abortifacient Agents
Mycophenolate mofetil
Methotrexate
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Disease
Neoplasms by Histologic Type
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 02, 2009