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

NCT01191957 | Completed Phase 3 DMC

• 1 other identifier: GITMO AMLR2
• Study Type: interventional
• Target: 252
• Locations: 2 countries
• Sites: 26

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:

• 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

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Acute Myeloid Leukemia; Allogeneic hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• transplant-related mortality (TRM)

  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.

  1 year post transplant

Secondary Outcomes (1)

• Assessment in the two arms of the safety and efficacy profile

  30-60-100-180 days, 1-2 years

Study Arms (2)

I. V. Busulphan plus Cyclophosphamide

ACTIVE COMPARATOR

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. Busulphan plus Fludarabine

EXPERIMENTAL

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

Interventions

Busulphan plus Cyclophosphamide DRUG

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

Also known as: I.V. BuCy2

I. V. Busulphan plus Cyclophosphamide

Busulphan plus Fludarabine DRUG

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

Also known as: I.V. BuFlu

I. V. Busulphan plus Fludarabine

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Gruppo Italiano Trapianto di Midollo Osseo: lead

Study Sites (26)

Chaim Sheba Medical Center

Tel Litwinsky, Israel

Location

Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Azienda Ospedaliera SS Antonio e Biagio

Alessandria, Italy

Location

Clinica di Ematologia - Ospedali Riuniti di Ancona

Ancona, Italy

Location

Policlinico di Bari-Ematologia con trapianti

Bari, Italy

Location

Ospedali Riuniti di Bergamo

Bergamo, 24128, Italy

Location

Ospedale Regionale Generale- Divisione Ematologia

Bolzano, Italy

Location

AO Spedali Civili di Brescia- USD - TMO Adulti

Brescia, Italy

Location

Ospedale Ferrarotto - Ematologia

Catania, Italy

Location

S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle

Cuneo, Italy

Location

Cattedra di Ematologia - Azienda Ospedaliera di Careggi

Florence, Italy

Location

AOU-IRCCS San Martino-IST Ematologia II

Genova, Italy

Location

Divisione di Ematologia - Istituto Nazionale dei Tumori

Milan, Italy

Location

U.O. Ematologia I - Centro Trapianti di Midollo - Ospedale Maggiore - Policlinico Mangiagalli e Regina Elena

Milan, Italy

Location

Cattedra di Medicina Interna ed Ematologia - Ospedale S. Gerardo de' i Tintori - Università degli Studi di Milano

Monza, Italy

Location

A.O.U. Policlinico Federico II

Napoli, Italy

Location

AOR Villa Sofia-Cervello - Bone Marrow Transplant Unit

Palermo, Italy

Location

IRCCS Policlinico S. Matteo

Pavia, Italy

Location

Dip. di Ematologia - Unità di Terapia Intensiva Ematologica per il Trapianto Emopoietico - Ospedale Civile di Pescara

Pescara, Italy

Location

Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli

Roma, Italy

Location

Policlinico Universitario Tor Vergata

Roma, Italy

Location

Sapienza University

Roma, Italy

Location

Az. Ospedaliera Universitaria Senese - Divisione Ematologia e Trapianti

Siena, Italy

Location

AOU Città della Salute e della Scienza

Torino, Italy

Location

Clinica Ematologica - Policlinico Universitario

Udine, Italy

Location

Ospedale S. Bortolo-Divisione Ematologia

Vicenza, Italy

Location

Related Publications (1)

• Rambaldi A, Grassi A, Masciulli A, Boschini C, Mico MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scime R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-1536. doi: 10.1016/S1470-2045(15)00200-4. Epub 2015 Sep 28.

  PMID: 26429297 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Busulfan; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Alessandro AR Rambaldi, Professor

  A.O. Papa Giovanni XXIII

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2010
• First Posted: August 31, 2010
• Study Start: January 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: October 1, 2014
• Last Updated: March 10, 2023

Record last verified: 2023-03

Locations

IT (25); IL (1)