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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Trapianto di Midollo Osseo
ClinicalTrials.gov Identifier:
NCT01191957
First received: June 10, 2010
Last updated: August 2, 2013
Last verified: June 2011
  Purpose

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 Intervention Phase
Acute Myeloid Leukemia (AML)
Drug: Busulphan plus Cyclophosphamide
Drug: Busulphan plus Fludarabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Trapianto di Midollo Osseo:

Primary Outcome Measures:
  • transplant-related mortality (TRM) [ Time Frame: 1 year post transplant ] [ Designated as safety issue: No ]

    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:
  • Assessment in the two arms of the safety and efficacy profile [ Time Frame: 30-60-100-180 days, 1-2 years ] [ Designated as safety issue: Yes ]
    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)


Estimated Enrollment: 240
Study Start Date: January 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

Patients

  • 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
  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: NCT01191957

Locations
Israel
Chaim Sheba Medical Center
Tel Hashomer, Israel
Italy
Azienda Ospedaliera SS Antonio e Biagio
Alessandria, Italy
Clinica di Ematologia - Ospedali Riuniti di Ancona
Ancona, Italy
Policlinico di Bari-Ematologia con trapianti
Bari, Italy
Ospedali Riuniti di Bergamo
Bergamo, Italy, 24128
Ospedale Regionale Generale- Divisione Ematologia
Bolzano, Italy
AO Spedali Civili di Brescia- USD - TMO Adulti
Brescia, Italy
Ospedale Ferrarotto - Ematologia
Catania, Italy
S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle
Cuneo, Italy
Cattedra di Ematologia - Azienda Ospedaliera di Careggi
Firenze, Italy
Trapianti Midollo Osseo - Div. di Ematologia 2 - Ospedale S. Martino
Genova, Italy
U.O. Ematologia I - Centro Trapianti di Midollo - Ospedale Maggiore - Policlinico Mangiagalli e Regina Elena
Milano, Italy
Divisione di Ematologia - Istituto Nazionale dei Tumori
Milano, Italy
Cattedra di Medicina Interna ed Ematologia - Ospedale S. Gerardo de' i Tintori - Università degli Studi di Milano
Monza, Italy
A.O.U. Policlinico Federico II
Napoli, Italy
Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara
Pescara, Italy
Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli
Roma, Italy
Policlinico Universitario Tor Vergata
Roma, Italy
Cattedra di Ematologia - Università La Sapienza
Roma, Italy
Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza
S. Giovanni Rotondo (FG), Italy
Az. Ospedaliera Universitaria Senese - Divisione Ematologia e Trapianti
Siena, Italy
Ematologia 2 - ASO San Giovanni Battista
Torino, Italy
Clinica Ematologica - Policlinico Universitario
Udine, Italy
Ospedale S. Bortolo-Divisione Ematologia
Vicenza, Italy
Sponsors and Collaborators
Gruppo Italiano Trapianto di Midollo Osseo
Investigators
Principal Investigator: Alessandro AR Rambaldi, Professor A.O. Papa Giovanni XXIII
  More Information

No publications provided

Responsible Party: Gruppo Italiano Trapianto di Midollo Osseo
ClinicalTrials.gov Identifier: NCT01191957     History of Changes
Other Study ID Numbers: GITMO AMLR2
Study First Received: June 10, 2010
Last Updated: August 2, 2013
Health Authority: Italy: Ethics Committee
Israel: Ethics Commission

Keywords provided by Gruppo Italiano Trapianto di Midollo Osseo:
Acute Myeloid Leukemia
Allogeneic hematopoietic stem cell transplantation

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Busulfan
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Vidarabine
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 21, 2014