RATIONALE: Colony-stimulating factors, such as filgrastim, stimulate the production of blood cells. Peripheral stem cell transplantation or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. Giving filgrastim to mobilize (stimulate) peripheral stem cells that can be collected for peripheral stem cell transplantation may result in fewer side effects after the transplant. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Methotrexate and cyclosporine or tacrolimus may prevent this from happening. It is not yet known whether filgrastim-mobilized donor peripheral stem cell transplantation is more effective than donor bone marrow transplantation in treating hematologic malignancies.

PURPOSE: Randomized phase III trial to compare the effectiveness of filgrastim-mobilized donor peripheral stem cell transplantation with that of donor bone marrow transplantation in treating patients who have hematologic cancer.

Condition	Treatment or Intervention	Phase
acute leukemia chronic leukemia chronic myeloproliferative disorders myelodysplastic and myeloproliferative disease	Drug: anti-thymocyte globulin  Drug: busulfan  Drug: cyclophosphamide  Drug: cyclosporine  Drug: fludarabine  Drug: melphalan  Drug: methotrexate  Drug: tacrolimus  Procedure: allogeneic bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: non-specific immune-modulator therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: supportive care/therapy	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare the 2-year survival rate in patients with hematologic malignancies treated with filgrastim (G-CSF)-mobilized peripheral blood stem cell (PBSC) transplantation vs bone marrow transplantation from HLA-compatible unrelated donors.

Secondary

• Compare the survival rate after transplantation in patients treated with these regimens.
• Compare the incidence of graft failure, acute graft-versus-host disease (GVHD), and chronic GVHD in patients treated with these regimens.
• Compare the time off all immunosuppressive therapy and immune reconstitution in patients treated with these regimens.
• Compare the incidence of neutrophil and platelet engraftment in patients treated with these regimens.
• Compare the incidence of relapse and infection in patients treated with these regimens.
• Compare the adverse events in patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.
• Correlate cell subsets in bone marrow or PBSC grafts with transplantation outcome in patients treated with these regimens.
• Compare the time to return to baseline functional score, toxicity score, and complete blood count and WBC differential values in donors contributing G-CSF-mobilized PBSCs vs bone marrow for these patients.
• Compare the donation experience, recovery, and quality of life of these donors.

OUTLINE: This is a partially randomized, open-label, multicenter study. Patients are stratified according to participating center and disease risk (good vs poor).

• All patients receive 1 of the following conditioning regimens, at the discretion of the participating center:
• Conditioning regimen A: Patients receive cyclophosphamide IV and total body irradiation.
• Conditioning regimen B: Patients receive busulfan orally or IV and cyclophosphamide IV.
• Conditioning regimen C: Patients receive fludarabine IV and melphalan IV.
• Conditioning regimen D: Patients receive fludarabine IV, busulfan orally or IV, and anti-thymocyte globulin IV.
• Patients are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.
• Arm II: Patients receive allogeneic bone marrow transplantation on day 0.
• Patients receive 1 of the following GVHD prophylaxis regimens, at the discretion of the participating center:
• GVHD regimen A: Beginning no later than day -1, patients receive cyclosporine IV and then orally daily followed by a taper beginning on approximately day 50 and continuing until approximately day 190. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
• GVHD regimen B: Beginning no later than day -1, patients receive tacrolimus IV and then orally daily followed by a taper beginning on approximately day 50 and continuing until approximately day 190. Patients also receive methotrexate as in GVHD regimen A. Patients who fail to achieve engraftment may receive an additional infusion of stem cells from the original donor or may undergo another transplantation from a different donor, at the discretion of the participating center.

Patients receive additional therapies (e.g., testicular irradiation, CNS prophylaxis, and/or donor lymphocyte infusions) as appropriate and at the discretion of the participating center.

Quality of life (QOL) is assessed in patients at baseline and at 6 months, 1 year, and 2 years post-transplantation. QOL is assessed in donors at baseline, on day 4 of G-CSF administration (for arm I donors), within 2 days after donation, weekly for 3 weeks, and then at 6 and 12 months.

Patients are followed weekly until day 100, at 4, 6, 7, 9, and 11 months, 1 year, and then annually for 2 years post-transplantation.

PROJECTED ACCRUAL: A total of 550-652 patients (275-326 per treatment arm) will be accrued for this study within 3 years.

Ages Eligible for Study:  up to  66 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of any of the following:
• Acute myeloid leukemia
• Not in remission OR in any remission
• Acute lymphoblastic leukemia
• Not in remission OR in any remission
• Chronic myelogenous leukemia
• Chronic phase meeting any of the following criteria:
• In hematologic remission
• No blast cells or precursor cells in peripheral blood or bone marrow
• In partial cytogenetic remission
• Ph-positive metaphases > 0% but < 35%
• In complete cytogenetic remission
• No Ph-positive metaphases
• Stable disease, but not in hematologic remission
• Blasts present in bone marrow and/or peripheral blood, however disease does not qualify as accelerated blast phase
• Accelerated phase with 1 of the following symptoms:
• WBC difficult to control (> 50,000/mm^3 with therapy)
• Rapid doubling of WBC (< 5 days)
• ≥ 10% blasts in blood or bone marrow
• ≥ 20% blasts and/or promyelocytes in blood or bone marrow
• ≥ 20% basophils and/or eosinophils in blood
• Anemia or thrombocytopenia unresponsive to standard therapy
• Persistent thrombocytosis (> 1,000/mm^3)
• Cytogenetic abnormalities in addition to Ph-positive
• Increasing splenomegaly
• Marrow fibrosis
• Blastic phase, meeting 1 of the following criteria:
• More than 30% blasts and/or promyelocytes in blood or bone marrow
• More than 20% blasts
• Myelodysplastic syndromes (MDS) of any of the following subtypes:
• Refractory anemia (RA)
• RA with ringed sideroblasts
• Refractory cytopenia with multilineage dysplasia
• Refractory cytopenia with multilineage dysplasia and ringed sideroblasts
• RA with excess blasts-1 (5-10% blasts)
• RA with excess blasts-2 (10-20% blasts)
• MDS, unclassifiable
• MDS associated with isolated del(5q)
• Myeloproliferative disorder of any of the following subtypes:
• Chronic myelomonocytic leukemia
• Agnogenic myeloid metaplasia with myelofibrosis (idiopathic myelofibrosis)
• Juvenile myelomonocytic leukemia
• No lymphoma or other malignant or nonmalignant disorders
• Must have an HLA 5/6 or 6/6 matched unrelated donor meeting the following criteria:
• At least 18 years old
• Matched for HLA-A, B, and DRB1 antigens
• One antigen mismatch at HLA-A, B, or DRB1 with or without mismatch at HLA-C is allowed

PATIENT CHARACTERISTICS: Age

• 66 and under

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin ≤ 2 times upper limit of normal* (ULN)
• ALT or AST ≤ 2 times ULN NOTE: *Except for isolated hyperbilirubinemia secondary to Gilbert's syndrome

Renal

• Creatinine ≤ 2 times ULN

Cardiovascular

• No cardiac insufficiency
• No coronary artery disease requiring treatment

Pulmonary

• FVC ≥ 50% of predicted*
• FEV_1 ≥ 50% of predicted*
• DLCO ≥ 50% of predicted* NOTE: *Corrected for hemoglobin

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No active infection requiring systemic therapy with antibacterial, antifungal, or antiviral agents

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior allogeneic or autologous hematopoietic stem cell transplantation

Chemotherapy

• Not specified

Endocrine therapy

• No concurrent glucocorticosteroids during graft-versus-host disease prophylaxis

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No concurrent enrollment in a phase I study

Arizona
      Banner Good Samaritan Medical Center, Phoenix,  Arizona,  85006,  United States; Recruiting
California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92037-0960,  United States; Recruiting
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5623,  United States; Recruiting
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
Florida
      University of Florida Shands Cancer Center, Gainesville,  Florida,  32610-100277,  United States; Recruiting
Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Illinois
      Children's Memorial Hospital - Chicago, Chicago,  Illinois,  60614,  United States; Recruiting
Indiana
      Indiana Blood and Marrow Transplantation, Indianapolis,  Indiana,  46237,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0922,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Missouri
      Kansas City Cancer Centers - Central, Kansas City,  Missouri,  64111,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
      St. Louis Children's Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States; Recruiting
New Jersey
      Cancer Center at Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States; Recruiting
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73190,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Pennsylvania
      Abramson Cancer Center at the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104-4283,  United States; Recruiting
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6310,  United States; Recruiting
Texas
      Charles A. Sammons Cancer Center, Dallas,  Texas,  75246,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
Utah
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112,  United States; Recruiting
Virginia
      Massey Cancer Center at Virginia Commonwealth University, Richmond,  Virginia,  23298-0037,  United States; Recruiting
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98104,  United States; Recruiting

Study chairs or principal investigators

Claudio Anasetti, MD,  Principal Investigator,  H. Lee Moffitt Cancer Center and Research Institute   

Study ID Numbers:  CDR0000349376; BMTCTN-0201; MAYO-215803; FHCRC-1860.00; NCT00075816
Record last reviewed:  September 2004
Last Updated:  April 4, 2005
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075816
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08