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

• Status: Completed
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gruppo Italiano Trapianto di Midollo Osseo
• Treatments: Busulfan; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine

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