Lymphoid Neoplasms, Myeloid Leukemia, Precursor Myeloid Neoplasms
Conditions
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.
Interventions
DRUGBusulfan-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.
DRUGCyclophosphamide-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.
Sponsors
University Hospital, Zürich
University Hospital, Geneva
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Liver toxicity | Day 30 | Liver toxicity, assessed as absolute serum values of ASAT, ALAT, GGT, Alkaline Phosphatase, bilirubin at day 30. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| VOD | Day 30 | Incidence and severity of veno occlusive disease (VOD) at day 30 |
| Efficacy | Day 30 and Day 100 | Survival, relapse and non-relapse mortality at day 30 and day 100 |
| Toxicity | Day 30 and Day 100 | Organ toxicity at day 30 and day 100 |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Switzerland
Outcome results
None listed