Clinical trial NCT01779882: Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT
Official title: Cyclophosphamide-Busulfan Versus Busulfan-Cyclophosphamide as Conditioning Regimen Before Allogeneic Hematopoietic Stem Cell Transplantation for Leukemia: a Prospective Randomized Study to Assess Liver Toxicity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Myeloid Leukemia
Precursor Myeloid Neoplasms
Lymphoid Neoplasms
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: University Hospital, Zürich
name: University Hospital, Geneva
First posted: 2013-01-30
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to test the hypothesis, that the order of application of Busulfan (BU) and Cyclophosphamide (CY) has an impact on toxicity after allogeneic Hematopoietic stem cell transplantation (HSCT) and that CY-BU reduces liver toxicity compared to BU-CY.


Eligibility criteria: Inclusion Criteria:

* Patients planned to undergo an allogeneic HSCT with myeloablative conditioning
* Age 18 - 65 years
* Myeloid leukemia respectively related precursor neoplasms (acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome), or lymphoid neoplasms (acute lymphoblastic leukemia/lymphoma, mature B-/T-/natural killer (NK)-cell neoplasms).
* Human Leukocyte Antigen (HLA)-identical sibling donor or matched unrelated (min. 10/10 Ag matched)
* Patients with a history of hepatitis might be included, if no contraindication for HSCT exists.
* Patient must give written informed consent

Exclusion Criteria:

* Indication other than myeloid leukemia respectively related precursor neoplasms, or lymphoid neoplasms.
* Severe liver damage for \> 2 weeks (bilirubin \> 3xupper limit normal (ULN) or ASAT/ALAT \> 5xULN)
* HIV infection
* Donor other than HLA-identical sibling or min. 10/10 matched unrelated donor
* Pregnant or lactating women
* Lack of written informed consent

Primary outcomes:
measure: Liver toxicity
timeFrame: Day 30
Secondary outcomes:
measure: VOD
timeFrame: Day 30
measure: Acute graft-versus-host disease (GvHD)
timeFrame: Day 30 and Day 100
measure: Toxicity
timeFrame: Day 30 and Day 100
measure: Efficacy
timeFrame: Day 30 and Day 100
measure: Cumulative liver values
timeFrame: Day 0, 10, 20 and 30
measure: Maximum liver values
timeFrame: Day 0, 10, 20 and 30
Other outcomes:
measure: Cytokines measurement
timeFrame: Day -8, 0, 10, 20 and 30
measure: Pharmacogenomics
timeFrame: Day -8, -3 and 0
Locations:
city: Basel
country: Switzerland
facility: University Hospital, Basel
city: Geneva
country: Switzerland
facility: University Hospital Geneva
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: Kantonsspital Aarau, Switzerland
name: Nathan Cantoni, MD
role: STUDY_CHAIR
affiliation: University Hospital, Basel, Switzerland
name: Sabine Gerull, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Zürich
name: Gayathri Nair, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Geneva, Switzerland
name: Yves Chalandon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Basel, Switzerland
name: Jakob Passweg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cantoni N, Gerull S, Heim D, Halter J, Bucher C, Buser A, Tsakiris DA, Passweg J, Tichelli A, Stern M, Gratwohl A. Order of application and liver toxicity in patients given BU and CY containing conditioning regimens for allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011 Mar;46(3):344-9. doi: 10.1038/bmt.2010.137. Epub 2010 Jun 14.