Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: BU-CY Group A (standard group): conditioning regimen with Busulfan (BU) followed by Cyclophosphamide (CY) |
Drug: Busulfan-Cyclophosphamide as Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation
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.
|
| Experimental: CY-BU Group B (experimental group): conditioning regimen with Cyclophosphamide (CY) followed by Busulfan (BU) |
Drug: Cyclophosphamide-Busulfan as Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation
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.
|
Outcome Measures
Primary Outcome Measures
- Liver toxicity [Day 30]
Liver toxicity, assessed as absolute serum values of ASAT, ALAT, GGT, Alkaline Phosphatase, bilirubin at day 30.
Secondary Outcome Measures
- VOD [Day 30]
Incidence and severity of "veno occlusive disease (VOD)" at day 30
- Acute graft-versus-host disease (GvHD) [Day 30 and Day 100]
Incidence and severity of acute GVHD, by organ (skin, liver, gut) at day 30 and day 100
- Toxicity [Day 30 and Day 100]
Organ toxicity at day 30 and day 100
- Efficacy [Day 30 and Day 100]
Survival, relapse and non-relapse mortality at day 30 and day 100
- Cumulative liver values [Day 0, 10, 20 and 30]
Cumulative serum values of aspartate transaminase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyltransferase (GGT), Alkaline Phosphatase, bilirubin for days 0, 10, 20 and 30
- Maximum liver values [Day 0, 10, 20 and 30]
Maximum serum values of ASAT, ALAT, GGT, alkaline phosphatase (AP), bilirubin at any time between day 0 and day 30
Other Outcome Measures
- Cytokines measurement [Day -8, 0, 10, 20 and 30]
To test the correlation between order of application of the conditioning regimen and the levels of proinflammatory cytokines as well as the correlation between levels of cytokines and development of acute GVHD, plasma samples will be collected at different time points.
- Pharmacogenomics [Day -8, -3 and 0]
The current hypothesis is that some functional polymorphisms of genes, which control important enzymes in BU and CY metabolism, contribute to the observed interindividual variability in toxicity after allogeneic HSCT.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients planned to undergo an allogeneic HSCT with myeloablative conditioning
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Age 18 - 65 years
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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).
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Human Leukocyte Antigen (HLA)-identical sibling donor or matched unrelated (min. 10/10 Ag matched)
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Patients with a history of hepatitis might be included, if no contraindication for HSCT exists.
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Patient must give written informed consent
Exclusion Criteria:
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Indication other than myeloid leukemia respectively related precursor neoplasms, or lymphoid neoplasms.
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Severe liver damage for > 2 weeks (bilirubin > 3xupper limit normal (ULN) or ASAT/ALAT
5xULN)
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HIV infection
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Donor other than HLA-identical sibling or min. 10/10 matched unrelated donor
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Pregnant or lactating women
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Lack of written informed consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital, Basel | Basel | Switzerland | 4031 | |
| 2 | University Hospital Geneva | Geneva | Switzerland | 1205 | |
| 3 | University Hospital Zurich | Zurich | Switzerland | 8091 |
Sponsors and Collaborators
- University Hospital, Basel, Switzerland
- University Hospital, Zürich
- University Hospital, Geneva
Investigators
- Study Chair: Nathan Cantoni, MD, Kantonsspital Aarau, Switzerland
- Principal Investigator: Sabine Gerull, MD, University Hospital, Basel, Switzerland
- Principal Investigator: Gayathri Nair, MD, University Hospital, Zürich
- Principal Investigator: Yves Chalandon, MD, University Hospital Geneva, Switzerland
- Principal Investigator: Jakob Passweg, MD, University Hospital, Basel, Switzerland
Study Documents (Full-Text)
None provided.More Information
Publications
- BuCyBu study