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Busulfan (BU) Plus Fludarabine Vs Intravenous BU Plus Cyclophosphamide as Conditioning Regimens Prior Allogeneic Hematopoetic Stem Cells Transplant (HSCT) in AML (GITMO-AMLR2)

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: NCT01191957
Recruitment Status : Completed
First Posted : August 31, 2010
Last Update Posted : August 20, 2021
Information provided by (Responsible Party):
Gruppo Italiano Trapianto di Midollo Osseo

Brief Summary:

The purpose of this prospective phase III, open-label, randomized multicenter study is to evaluate whether Acute Myeloid Leukemia (AML) elderly patients in Complete Remission (CR) undergoing allogeneic hematopoietic stem cell transplantation after a reduce toxicity conditioning regimen (I.V. BuFlu) as compared to the conventional I.V.

BuCy2 program will experience:

  1. A lower transplant-related mortality (TRM) at 1 year after Hematopoietic Stem Cells Transplant (HSCT)
  2. A similar anti-leukemic activity and a similar or better safety profile, in terms of:

    • Early and/or late graft rejection
    • Hematopoietic and immunologic recovery
    • Chimerism
    • Toxicity and incidence of Veno-occlusive Disease (VOD)
    • Acute (aGvHD) and chronic graft-versus-host disease (cGvHD)
    • Cumulative incidence of TRM at +100 days and 2 years after transplant
    • Cumulative incidence of relapse by 1 and 2 years after transplant
    • Event-free (EFS) and overall survival (OS) by 1 and 2 years after transplant

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Drug: Busulphan plus Cyclophosphamide Drug: Busulphan plus Fludarabine Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 252 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Study Comparing i.v. Busulfan (Busilvex®) Plus Fludarabine (BuFlu) Versus Busilvex® Plus Cyclophosphamide (BuCy2) as Conditioning Regimens Prior AlloHSCT in Patients (Age >= 40 and =<65 Years) With AML in Complete Remission.
Study Start Date : January 2008
Actual Primary Completion Date : December 2012
Actual Study Completion Date : October 2014

Arm Intervention/treatment
Active Comparator: I. V. Busulphan plus Cyclophosphamide
Conventional conditioning regimen with intravenous (i.v.) Busulphan (Busilvex), 12.8 mg/kg followed by Cyclophosphamide, 120 mg/kg iv.
Drug: Busulphan plus Cyclophosphamide

I.V. Bu (Busilvex), 12.8 mg/kg:

Day -9: 0.8 mg/kg/dose x 4 doses Day -8: 0.8 mg/kg/dose x 4 doses Day -7: 0.8 mg/kg/dose x 4 doses Day -6: 0.8 mg/kg/dose x 4 doses Day -5: Rest

Followed by:

Cyclophosphamide, 120 mg/kg iv:

Day -4: 60 mg/kg Day -3: 60 mg/kg

Other Name: I.V. BuCy2

Experimental: I. V. Busulphan plus Fludarabine
Reduced toxicity conditioning regimen with intravenous (i.v.)Busulphan (Busilvex), 12.8 mg/kg plus Fludarabine, 4 x 40 mg/m².
Drug: Busulphan plus Fludarabine

I.V. Bu (Busilvex), 12.8 mg/kg:

Day -6: 0.8 mg/kg/dose x 4 doses Day -5: 0.8 mg/kg/dose x 4 doses Day -4: 0.8 mg/kg/dose x 4 doses Day -3: 0.8 mg/kg/dose x 4 doses plus:

Fludarabine, 4 x 40 mg/m² iv:

Day -6: 40 mg/m² Day -5: 40 mg/m² Day -4: 40 mg/m² Day -3: 40 mg/m²

Other Name: I.V. BuFlu

Primary Outcome Measures :
  1. transplant-related mortality (TRM) [ Time Frame: 1 year post transplant ]

    The primary endpoint is to determine the cumulative incidence of transplant related mortality (TRM) defined as non-relapse mortality. Assessment will be performed at 1 year after transplantation.

    TRM will be defined as any death by causes other than relapse and/or progressive disease. Deaths after persistent post-transplant relapse will be categorized as due to the disease irrespective of the proximate cause.

Secondary Outcome Measures :
  1. Assessment in the two arms of the safety and efficacy profile [ Time Frame: 30-60-100-180 days, 1-2 years ]
    Assessment in the two arms of the safety and efficacy profile defined as: early and/or late graft rejection, hematopoietic recovery, chimerism, toxicity and incidence of VOD, incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD), cumulative incidence of TRM, relapse, event-free (EFS) and overall survival (OS)

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients
  • Age more than 40 and less than 65 years
  • Diagnosis of AML (FAB or WHO classification) in Complete Remission (CR)
  • Availability of an HLA compatible sibling or unrelated donor
  • Performance status : Eastern Cooperative Oncology Group (ECOG)<3
  • Written and signed informed consent
  • Central Venous access (Central KT) secured through an indwelling catheter.
  • Life expectancy not severely limited by concomitant illness. Donors
  • Age between 18 years and 65 years inclusive.
  • Availability of an HLA-identical sibling donor (MRD) or HLA-compatible unrelated donor (MUD). Donor selection is based on molecular high-resolution typing (4 digits) of the HLA gene loci class I (HLA- A, B, and C) and class II (DRB1). In case, no class I and class II completely identical donor (8 out of 8 gene loci) can be identified, one antigen/allele disparity (class I) or one allele disparity (class II, DRB1) between patient and donor are acceptable. In any cases the degree of histocompatibility between patient and donor must fulfill with the minimal degree of matching established by the Italian Bone Marrow Donor Registry.

Exclusion Criteria:


  • AML patients in 1st CR with:

    • t(15;17) or promyelocytic leukemia/retinoic acid receptor gene translocation, PML/RARα positive APL
    • t(8;21)(q22;q22) with white blood cells (WBC) count at diagnosis less than 20 x 109/L without additional adverse cytogenetic abnormalities.
    • inv(16) or t(16;16)(p13;q22) without additional adverse cytogenetic abnormalities.
  • Previous allogeneic transplantation Poorly controlled arterial hypertension with blood pressure above 150/90 on standard medication
  • Acute Myocardial Infarction (AMI) within the last 12 months
  • Positive pregnancy test (in women not in menopause)
  • Positive HIV serology
  • Any major organ dysfunction
  • Pulmonary dysfunction (Fraction Ejection Volume, FEV1 <40%, Diffusing Capacity of Lung for carbon monoxide, DLCO <50%,)
  • Hepatic dysfunction (Serum bilirubin >1.5 mg% or serum transaminases >2x UNL)
  • Chronic active hepatitis or cirrhosis
  • Cardiac dysfunction (LVEF <40)
  • Chronic renal insufficiency (Serum creatinine >1.5 mg/dl or creatinine clearance <=50 ml/min)
  • Invasive fungal infection still evolutive at the time of registration
  • Central nervous system involvement
  • Uncontrolled oral/dental infections
  • Abnormal dental evaluation
  • Patient has another progressive malignant disease or a history of other malignancies within 2 years prior to study entry
  • Severe psychiatric illness or any disorder that compromises ability to give truly informed consent for participation in this study

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): NCT01191957

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Sponsors and Collaborators
Gruppo Italiano Trapianto di Midollo Osseo
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Principal Investigator: Alessandro AR Rambaldi, Professor A.O. Papa Giovanni XXIII
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Gruppo Italiano Trapianto di Midollo Osseo Identifier: NCT01191957    
Other Study ID Numbers: GITMO AMLR2
First Posted: August 31, 2010    Key Record Dates
Last Update Posted: August 20, 2021
Last Verified: August 2021
Keywords provided by Gruppo Italiano Trapianto di Midollo Osseo:
Acute Myeloid Leukemia
Allogeneic hematopoietic stem cell transplantation
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists