Trial record 1 of 2 for:    BMT CTN 0901
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Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01339910
Recruitment Status : Terminated (Accrual terminated as recommended by the data and safety monitoring board.)
First Posted : April 21, 2011
Last Update Posted : December 2, 2017
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Blood and Marrow Transplant Clinical Trials Network
National Marrow Donor Program
Information provided by (Responsible Party):
Medical College of Wisconsin

Brief Summary:
The study is designed as a Phase III, multicenter trial comparing outcomes after allogeneic hematopoietic stem cell transplantation (HCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) between patients receiving myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC) regimens.

Condition or disease Intervention/treatment Phase
Leukemia, Myelocytic, Acute Drug: Fludarabine and Busulfan Drug: Fludarabine and Melphalan Drug: Busulfan and Fludarabine Drug: Busulfan and Cyclophosphamide Drug: Cyclophosphamide and Total Body Irradiation Phase 3

Detailed Description:
Patients randomized to RIC will receive one of two regimen types: the combination of fludarabine (120-180 mg/m^2) and busulfan (less than or equal to 8 mg/kg or IV equivalent) (Flu/Bu) or fludarabine (120-180 mg/m^2) and melphalan (less than 150 mg/m^2) (Flu/Mel). Patient randomized to MAC will receive one of three regimens: busulfan (16 mg/kg oral or 12.8 mg/kg IV equivalent) and cyclophosphamide (120 mg/kg) (Bu/Cy); or, busulfan (16 mg/kg PO or 12.8 mg/kg IV) and fludarabine (120-180 mg/m^2) (Bu/Flu); or, cyclophosphamide (120 mg/kg) and total body irradiation (greater than 1200-1420cGy) (CyTBI). A total of 356 patients (178 to each arm) will be accrued on this study over a period of four years. Patients will be followed for up to 18 months from transplantation.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 272 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Multi-Center, Phase III Study of Allogeneic Stem Cell Transplantation Comparing Regimen Intensity in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia (BMT CTN #0901)
Actual Study Start Date : May 2011
Actual Primary Completion Date : January 16, 2017
Actual Study Completion Date : October 16, 2017

Arm Intervention/treatment
Active Comparator: Reduced Intensity Conditioning (RIC)
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Drug: Fludarabine and Busulfan


  • Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2)
  • Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Other Name: Fludara and Busulfex
Drug: Fludarabine and Melphalan


  • Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2)
  • Melphalan: 140 mg/m^2 on Day -2
Other Name: Fludara and Alkeran
Experimental: Myeloablative Conditioning Regimen (MAC)
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Drug: Busulfan and Fludarabine


  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2
  • Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2)
Other Name: Busulfex and Fludara
Drug: Busulfan and Cyclophosphamide


  • Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Other Name: Busulfex and Cytoxan
Drug: Cyclophosphamide and Total Body Irradiation


  • TBI: 1200-1420 cGy on Days -7 to -4
  • Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Other Name: Cytoxan and radiation

Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 18 months ]
    The primary objective of the trial is to compare 18 month overall survival rates of the two groups of patients starting from the time of randomization to the RIC or MAC arms.

Secondary Outcome Measures :
  1. Disease-Free Survival [ Time Frame: time from randomization to relapse, death, initiation of non-protocol AML or MDS therapy, loss to follow up or end of study whichever comes first ]
    Disease-free survival will be at different time points. Patients are considered a failure if they die or suffer from disease relapse.

  2. Treatment-related Mortality [ Time Frame: 18 months ]
    Treatment-related mortality (TRM) is defined as death occurring in a patient from causes other than disease relapse. Individuals who relapse are censored for the event of TRM.

  3. Neutrophil and Platelet Engraftment [ Time Frame: 100 days ]
    Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500 µL for 3 consecutive measurements on different days. The first of the 3 days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 20,000 and 50,000/µL for consecutive measurements over 7 days without requiring platelet transfusions. The first of the 7 days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 7 days.

  4. Donor Cell Engraftment [ Time Frame: Day 100 and 18 months post transplantation ]
    Donor cell engraftment will be assessed by donor recipient chimerism studies. For this protocol, mixed chimerism will be defined as the presence of donor cells, as a proportion of the total population of less than 95% in the peripheral blood or bone marrow. Full donor chimerism is defined as greater than 95% donor donor cells. Mixed or full donor chimerism will be evidence of donor engraftment. For this protocol, graft rejection is defined as the inability to detect or loss of detection of greater than 5% donor cells as a proportion of the total population.

  5. Acute Graft Versus Host Disease (GVHD) of Grades II-IV and III-IV [ Time Frame: 100 days ]
    The first day of acute GVHD onset at a certain grade will be used to calculate cumulative incidence curves for that GVHD grade (e.g., if the onset of grade I acute GVHD is on Day 19 post-transplant and onset of grade III is on Day 70 post-transplant, time to grade III is Day 70). This endpoint will be evaluated through 100 days and compared between treatment arms.

  6. Chronic GVHD [ Time Frame: 18 months ]
    The first day of chronic GVHD onset will be used to calculate cumulative incidence curves. Rates and severity of chronic GVHD will be compared between treatment arms.

  7. Incidence of Primary Graft Failure [ Time Frame: 28 days ]
    This is defined by lack of neutrophil engraftment by 28 days. Rates of primary graft failure will be compared between treatment arms.

  8. Incidence of Secondary Graft Failure [ Time Frame: 18 months ]
    This is defined by initial neutrophil engraftment followed by subsequent decline in neutrophil counts less than 500/µL unresponsive to growth factor therapy. Rates of secondary graft failure will be compared between treatment arms.

  9. Incidence of Toxicities Greater Than Grade 3 [ Time Frame: 18 months ]
    All toxicities greater than or equal to Grade 3 will be tabulated by grade for each treatment arm, by type of toxicity as well as the peak grade overall. Toxicity frequencies will be described for each time interval as well as cumulative over time.

  10. Incidence of Infections [ Time Frame: 6, 12, and 18 months post transplant or until death ]
    The number of infections and the number of patients experiencing infections will be tabulated by type of infection, severity, and time period after transplant. The cumulative incidence of severe, life-threatening, or fatal infections will be compared between the two treatment arms at 6, 12, and 18 months from transplant or until death.

  11. Immune Reconstitution [ Time Frame: Baseline, 100 days, 12 months and 18 months post transplant ]
    Quantitative assessments of peripheral blood CD3, CD4, CD8, CD19 and CD56 positive lymphocytes will be done through flow cytometric analysis at baseline , 100 days, 12 months and 18 months post transplantation. Results will be tabulated according to time from transplant.

  12. Health-related Quality of Life (HQL) [ Time Frame: Prior to transplant, 100 days, 12 and 18 months or until death ]
    HQL will be described and compared between the two treatment arms over time. The self report questionnaires will be completed prior to transplantation and subsequently at 100 days, 12, and 18 months from randomization or until death. HQL include: FACT-BMT, SF-36, MDASI and EQ-5D.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age equal or less than 65 years old and equal to or greater than 18 years old.
  • Patients with the diagnosis of MDS or AML with fewer than 5% myeloblasts in the bone marrow and no leukemic myeloblasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen enrollment.
  • For patients receiving treatment of their MDS or AML prior to transplantation: a)Interval between the start of the most recent cycle of conventional cytotoxic chemotherapy and enrollment must be at least 30 days; b)Interval between completing treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and enrollment must be at least 10 days.
  • Patients must have a related or unrelated bone marrow or peripheral blood donor who is human leukocyte antigen (HLA)-matched at 7 or 8 of 8 HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.
  • HCT-Specific Comorbidity Index Score (HCT-CI) less than or equal to 4.
  • Organ function: a) Cardiac function: Ejection fraction greater than or equal to 40%; b) Hepatic function: total bilirubin less than or equal to 2 times the upper limit of normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 times the upper limit of normal.; c)Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) greater than or equal to 40% and forced expiratory volume in one second (FEV1) greater than or equal to 50% (corrected for hemoglobin).
  • Creatinine clearance greater than or equal to 50mL/min based on the Cockcroft-Gault formula.
  • Signed informed consent.

Exclusion Criteria:

  • Prior allograft or prior autograft.
  • Symptomatic coronary artery disease.
  • Leukemia involvement in the central nervous system (CNS) within 4 weeks of enrollment for patients with a history of prior CNS leukemia involvement (i.e., leukemic blasts previously detected in the cerebral spinal fluid).
  • Karnofsky Performance Score less than 70.
  • Patients receiving supplemental oxygen.
  • Planned use of donor lymphocyte infusion (DLI) therapy.
  • Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms).
  • Patients seropositive for the human immunodeficiency virus (HIV).
  • Patients with prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent greater than 5 years previously. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
  • Females who are pregnant or breastfeeding.
  • Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01339910

  Hide Study Locations
United States, Arizona
Mayo Clinic Phoenix
Phoenix, Arizona, United States, 85054
United States, California
University of California, San Diego Medical Center
La Jolla, California, United States, 92093
United States, Florida
University of Florida College of Medicine
Gainesville, Florida, United States, 32610-0277
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33624
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Blood and Marrow Transplant Program at Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Kansas
University of Kansas
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Massachusetts
DFCI, Brigham & Women's Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55095
United States, Missouri
Washington University/Barnes Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Mount Sinai Medical Center
New York, New York, United States, 10029
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
University of North Carolina Hospital at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Ohio
Jewish Hospital BMT Program
Cincinnati, Ohio, United States, 45236
University Hospitals of Cleveland/Case Western
Cleveland, Ohio, United States, 44106-5061
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Utah
Utah BMT/University of Utah Medical School
Salt Lake City, Utah, United States, 84132
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
United States, West Virginia
West Virginia University Hospital
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
University of Wisconsin Hospital & Clinics
Madison, Wisconsin, United States, 53792-5156
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53211
Sponsors and Collaborators
Medical College of Wisconsin
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Blood and Marrow Transplant Clinical Trials Network
National Marrow Donor Program
Study Director: Mary Horowitz, MD Center for International Blood and Marrow Transplant Research

Additional Information:
Responsible Party: Medical College of Wisconsin Identifier: NCT01339910     History of Changes
Other Study ID Numbers: BMTCTN0901
U01HL069294 ( U.S. NIH Grant/Contract )
U01HL069294-05 ( U.S. NIH Grant/Contract )
BMT CTN 0901 ( Other Identifier: Blood and Marrow Transplant Clinical Trial Network )
5U24CA076518 ( U.S. NIH Grant/Contract )
First Posted: April 21, 2011    Key Record Dates
Last Update Posted: December 2, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Findings will be published in a manuscript
Time Frame: Within 6 months of official study closure at participating sites.
Access Criteria: Available to the public.

Keywords provided by Medical College of Wisconsin:
Acute Myelogenous Leukemia
Myelodysplastic Syndrome

Additional relevant MeSH terms:
Leukemia, Myeloid
Myelodysplastic Syndromes
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents