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Leukemia, Myelocytic, AcutePhase 3NCT01339910

Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)

A Phase 3 study testing Fludarabine and Busulfan, Fludarabine and Melphalan and Busulfan and Fludarabine in people with Leukemia, Myelocytic, Acute, run by Medical College of Wisconsin at 32 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Leukemia, Myelocytic, Acute
What is being tested?
Fludarabine and Busulfan, Fludarabine and Melphalan and Busulfan and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
272 participants
Where
32 sitesUnited States
Study dates
Jun 2011to 16 Oct 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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.

Trial locations and contacts

32 sites in 1 country.

32 sites in 1 country

United States32 sites

  • Emory University

    Atlanta, Georgia, 30322

  • Blood and Marrow Transplant Program at Northside Hospital

    Atlanta, Georgia, 30342

  • DFCI, Brigham & Women's Hospital

    Boston, Massachusetts, 02114

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of North Carolina Hospital at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Jewish Hospital BMT Program

    Cincinnati, Ohio, 45236

  • University Hospitals of Cleveland/Case Western

    Cleveland, Ohio, 44106-5061

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • University of Florida College of Medicine

    Gainesville, Florida, 32610-0277

  • University of Kansas

    Kansas City, Kansas, 66160

  • University of California, San Diego Medical Center

    La Jolla, California, 92093

  • University of Kentucky

    Lexington, Kentucky, 40536

  • University of Wisconsin Hospital & Clinics

    Madison, Wisconsin, 53792-5156

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53211

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • West Virginia University Hospital

    Morgantown, West Virginia, 26506

  • Mount Sinai Medical Center

    New York, New York, 10029

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Florida Hospital Cancer Institute

    Orlando, Florida, 32804

  • University of Pennsylvania Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic Phoenix

    Phoenix, Arizona, 85054

  • Oregon Health & Science University

    Portland, Oregon, 97239-3098

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55095

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • Utah BMT/University of Utah Medical School

    Salt Lake City, Utah, 84132

  • Texas Transplant Institute

    San Antonio, Texas, 78229

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Washington University/Barnes Jewish Hospital

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33624

Other trials in United States

About this study

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)

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.

Read the 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.

Being tested
Fludarabine and Busulfan, Fludarabine and Melphalan, Busulfan and Fludarabine, Busulfan and Cyclophosphamide, Cyclophosphamide and Total Body Irradiation
Keywords
Acute Myelogenous Leukemia, Myelodysplastic Syndrome
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fludarabine and BusulfanDrug

    Also called Fludara and Busulfex

    (Flu/Bu)

    • 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

  • Fludarabine and MelphalanDrug

    Also called Fludara and Alkeran

    (Flu/Mel)

    • 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

  • Busulfan and FludarabineDrug

    Also called Busulfex and Fludara

    (Bu/Flu)

    • 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)

  • Busulfan and CyclophosphamideDrug

    Also called Busulfex and Cytoxan

    (Bu/Cy)

    • 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)

  • Cyclophosphamide and Total Body IrradiationDrug

    Also called Cytoxan and radiation

    (Cy/TBI)

    • 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)
Study groups in NCT01339910
Study groupRoleWhat they receive
Reduced Intensity Conditioning (RIC)ExperimentalOne of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Receives: Drug: Fludarabine and Busulfan; Drug: Fludarabine and Melphalan
Myeloablative Conditioning Regimen (MAC)Active comparatorOne of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Receives: Drug: Busulfan and Fludarabine; Drug: Busulfan and Cyclophosphamide; Drug: Cyclophosphamide and Total Body Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Overall Survival (OS)

    Overall survival is defined as survival of death from any cause.

    Measured: 18 months post-randomization

Secondary outcomes (14)

  1. Percentage of Participants With Relapse-Free Survival (RFS)

    Relapse-free survival is defined as survival without relapse of the primary disease.

    Measured: 18 months post-randomization

  2. Percentage of Participants With Disease Relapse

    Disease Relapse is defined as relapse of the primary disease.

    Measured: 18 months post-randomization

  3. Percentage of Participants With Treatment-related Mortality

    Treatment-related mortality is defined as death without a previous relapse of the primary disease.

    Measured: 18 months post-randomization

  4. Percentage of Participants With Neutrophil and Platelet Engraftment

    Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10^6/liter 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/microliter 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.

    Measured: Days 28 and 60 post-transplant

  5. Number of Participants With Donor Cell Engraftment

    Donor cell engraftment will be assessed by donor-recipient chimerism assays. Full donor chimerism is defined as the presence of at least 95% donor cells as a proportion of the total population in the peripheral blood or bone marrow. Graft rejection is defined as the presence of no more than 5% donor cells as a proportion of the total population. Mixed chimerism is defined as the presence of between 5% and 95% donor cells. Mixed or full donor chimerism will be considered evidence of donor engraftment.

    Measured: Days 28 and 100 and 18 months post-transplant

  6. Percentage of Participants With Acute Graft Versus Host Disease (GVHD)

    Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:

    Skin stage:

    0: No rash

    1. Rash <25% of body surface area
    2. Rash on 25-50% of body surface area
    3. Rash on > 50% of body surface area
    4. Generalized erythroderma with bullous formation

    Liver stage (based on bilirubin level)*:

    0: <2 mg/dL

    1. 2-3 mg/dL
    2. 3.01-6 mg/dL
    3. 6.01-15.0 mg/dL
    4. >15 mg/dL

    GI stage*:

    0: No diarrhea or diarrhea <500 mL/day

    1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
    2. Diarrhea 1000-1499 mL/day
    3. Diarrhea >1500 mL/day
    4. Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.

    GVHD grade:

    0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

    Measured: Day 100 post-transplant

  7. Percentage of Participants With Chronic GVHD

    Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.

    Measured: 18 months post-transplant

  8. Number of Participants With Chronic GVHD Severity

    Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.

    Measured: 18 months post-transplant

  9. Number of Participants With Primary Graft Failure

    Primary graft failure is defined by lack of neutrophil engraftment.

    Measured: 28 days post-transplant

  10. Number of Participants With Secondary Graft Failure

    Secondary graft failure is defined by initial neutrophil engraftment followed by subsequent decline in neutrophil counts to less than 500x10^6/liter that is unresponsive to growth factor therapy.

    Measured: 18 months post-transplant

  11. Number of Participants With Maximum Grade 3-5 Toxicities

    The maximum grade of toxicities reported by participants over the study duration are tabulated. Per the CTCAE criteria, toxicities are graded on a scale of 0-5, with higher numbers indicating greater severity. The categories correspond as follows:

    3 - severe; 4 - life-threatening; 5 - fatal

    Measured: 18 months

  12. Infection Type

    The number and types of infection events reported are tabulated.

    Measured: 18 months post-transplant

  13. Number of Participants With Infections

    The maximum severity of infections reported by participants are tabulated.

    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.

    Measured: 18 months post-transplant

  14. Number of Participants With Cause of Death

    Primary cause of death was adjudicated using previously described criteria (Copelan et al. 2007). When relapse occurred, it was considered the primary cause of death regardless of other events.

    Measured: 18 months post-randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2011 (estimated)
  2. Study startJun 2011
  3. Primary completion16 Jan 2017
  4. Study completion16 Oct 2017

Why it stopped: Accrual terminated as recommended by the data and safety monitoring board.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
272 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01339910
Sponsor's protocol ID
BMTCTN0901
Other IDs
U01HL069294, U01HL069294-05, BMT CTN 0901, 5U24CA076518
Status last verified
Dec 2022
First submitted
20 Apr 2011
Last updated
4 Jan 2023
Data monitoring committee
Yes
Individual data sharing
Yes: Findings will be published in a manuscript

Publications

  • Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009 Jul 30;114(5):937-51. doi: 10.1182/blood-2009-03-209262. Epub 2009 Apr 8.

    PubMed 19357394

  • Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005 Oct 15;106(8):2912-9. doi: 10.1182/blood-2005-05-2004. Epub 2005 Jun 30.

    PubMed 15994282

  • Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.

    PubMed 16338616

  • Copelan E, Casper JT, Carter SL, van Burik JA, Hurd D, Mendizabal AM, Wagner JE, Yanovich S, Kernan NA. A scheme for defining cause of death and its application in the T cell depletion trial. Biol Blood Marrow Transplant. 2007 Dec;13(12):1469-76. doi: 10.1016/j.bbmt.2007.08.047.

    PubMed 18022577

  • Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. doi: 10.1200/JCO.2016.70.7091. Epub 2017 Feb 13.

    PubMed 28380315

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fludarabine and Busulfan, Fludarabine and Melphalan and Busulfan and Fludarabine in people with Leukemia, Myelocytic, Acute, run by Medical College of Wisconsin at 32 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Overall Survival (OS) (time frame: 18 months post-randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01339910, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2023.

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