Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000997257
Ethics application status
Approved
Date submitted
3/11/2009
Date registered
18/11/2009
Date last updated
11/05/2010
Type of registration
Retrospectively registered

Titles & IDs
Public title
Randomized Study Comparing Intravenous Busulfan (i.v. Bu; Busilvex [Registered Trademark]) plus Fludarabine (Buflu) Versus Intravenous Busulfan Plus Cyclophosphamide (Bucy2) As Conditioning Regimens Prior To Allogeneic Hematopoietic Stem Cell Transplantation (ALLOHSCT) In Patients (from 40 to 55 years) With Acute Myeloid Leukemia (AML) In Complete Remission (CR).
Scientific title
Busilvex plus Fludarabine Vs Busilvex plus Cyclophosphamide prior allogeneic transplantation in Acure Myeloid Leukimia (AML) to evaluate the transplant-related mortality.
Universal Trial Number (UTN)
Trial acronym
Gruppo Italiano Trapianto Midollo Osseo (GITMO) AML.R2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia (AML) 252115 0
Condition category
Condition code
Blood 252320 252320 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The purpose of this prospective phase III, open-label, randomized multi-center study is to evaluate
whether AML elderly patients in CR undergoing allogeneic hematopoietic stem cell transplantation (HSCT)
after a reduce toxicity conditioning regimen I.V. BuFlu [I.V. Bu (Busilvex), 12.8 mg/kg four times a day, for four days, plus Fludarabine, 40 mg/m² i.v. one time a day for four days] as compared to the conventional I.V.
BuCy2 program [I.V. Bu (Busilvex), 12.8 mg/kg, four times a day, for four days, followed by Cyclophosphamide, 60 mg/kg iv one time a day for two days] will experience:
1. A lower transplant-related mortality (TRM) at 1 year after allogenic stem cell transplantation (HSCT)
2. A similar anti-leukemic activity and a similar or better safety profile
Intervention code [1] 241498 0
Treatment: Drugs
Intervention code [2] 241499 0
Other interventions
Comparator / control treatment
Conditioning regimen (prior allogeneic transplant) with I.V. Bu (Busilvex), 12.8 mg/kg followed by Cyclophosphamide, 120 mg/kg iv
Control group
Active

Outcomes
Primary outcome [1] 253266 0
Transplant related mortality
Timepoint [1] 253266 0
1 year from transplant
Secondary outcome [1] 262259 0
Graft rejection and graft failure
Timepoint [1] 262259 0
by day +100, and 1 and 2 years after transplantation
Secondary outcome [2] 262260 0
Hematopoietic and immunologic recovery after transplantation
Timepoint [2] 262260 0
Time to reach an absolute neutrophil count > 0.5 109/L from recipient Day 0 (from the day of
graft infusion).
Time to reach platelet engraftment
Secondary outcome [3] 262261 0
Chimerism
Timepoint [3] 262261 0
at day + 30, +60, +100, +180, 1 year and 2 years.
Secondary outcome [4] 262262 0
Graft-versus-Host Disease (GvHD)
Timepoint [4] 262262 0
by day +100 post-transplant

Eligibility
Key inclusion criteria
Patients
- Age = between 40 and 55
- Diagnosis of acute myeloid Leukimia (AML) (Francese-Americana-Britannica or Word Healt Organization classification) in Complete Remission (CR)
- Availability of an HLA compatible sibling or unrelated donor
- Performance status : Eastern Cooperative Oncology Group code(ECOG)<3
- Written and signed informed consent
- Central Venous access secured through an indwelling catheter.
- Life expectancy not severely limited by concomitant illness.
Donors
- Age between 18 years and 65 years inclusive.
- Donors are assessed by HLA-A, -B, -C, -DRB1, DQB1 high-resolution typing and can be either
- HLA identical sibling or HLA phenotypically identical family donor
or
- HLA-matched unrelated with one allele mismatched (Class I or II).
Minimum age
40 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients
- AML patients in 1st CR with:
- t(15;17) or mutation of gene called PML/RARa positive Acute Promyelocytic Leukimia
- t(8;21)(q22;q22) with White Blood Cell 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 Human Immunodeficiency Virus (HIV) serology
- Any major organ dysfunction
Pulmonary dysfunction (Forced Expiratory Volume in One Second (FEV1) <40%, Diffusion Capacity Lung Oxigen (DLCO test) <50%,)
- Hepatic dysfunction (Serum bilirubin >1.5 mg% or serum transaminases >2)
- Chronic active hepatitis or cirrhosis
- Cardiac dysfunction (left ventricular ejection fraction (LVEF) <40)
- Chronic renal insufficiency (Serum creatinine >1.5 mg/dl or creatinine cleareance <=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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/01/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
240
Accrual to date
Final
Recruitment outside Australia
Country [1] 2306 0
Italy
State/province [1] 2306 0

Funding & Sponsors
Funding source category [1] 243964 0
Government body
Name [1] 243964 0
Agenzia Italiana del Farmaco
Country [1] 243964 0
Italy
Primary sponsor type
Other Collaborative groups
Name
GITMO (Gruppo Italiano Trapianto Midollo Osseo)
Address
A.O. Ospedali Riuniti di Bergamo
Largo Barozzi, 1
24128 Bergamo
Country
Italy
Secondary sponsor category [1] 251318 0
None
Name [1] 251318 0
Address [1] 251318 0
Country [1] 251318 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 244080 0
Comitato Etico Ospedali Riuniti di Bergamo
Ethics committee address [1] 244080 0
A.O. Ospedali Riuniti di Bergamo
Largo Barozzi, 1
24128 Bergamo
Ethics committee country [1] 244080 0
Italy
Date submitted for ethics approval [1] 244080 0
20/10/2007
Approval date [1] 244080 0
12/11/2007
Ethics approval number [1] 244080 0

Summary
Brief summary
The purpose of this prospective phase III, open-label, randomized multi-center study is to evaluate one year transplant-related mortality (TRM) of AML patients undergoing allogeneic hematopoietic
stem cell transplantation after a reduced toxicity conditioning regimen (I.V.BuFlu) as compared to
the conventional I.V. BuCy2 program
Trial website
https://heart.negrisud.it/gitmoamlr2
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30459 0
Address 30459 0
Country 30459 0
Phone 30459 0
Fax 30459 0
Email 30459 0
Contact person for public queries
Name 13706 0
Arianna Masciulli
Address 13706 0
Via Nazionale 8/A 66030, Santa Maria Imbaro (Chieti)
Country 13706 0
Italy
Phone 13706 0
0039-0872 570286
Fax 13706 0
0039-0872 570206
Email 13706 0
[email protected]
Contact person for scientific queries
Name 4634 0
Arianna Masciulli
Address 4634 0
Via Nazionale 8/A 66030, Santa Maria Imbaro (Chieti)
Country 4634 0
Italy
Phone 4634 0
0039-0872 570286
Fax 4634 0
0039-0872 570206
Email 4634 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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