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

This study has suspended participant recruitment.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00045305
First received: September 6, 2002
Last updated: July 11, 2012
Last verified: September 2009
  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 2

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:


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: November 2012 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Selina M. Luger, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

Additional Information:
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: July 11, 2012
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-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Methotrexate
Mycophenolate mofetil
Mycophenolic Acid
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014