Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT

Study Overview
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Brief Summary
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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.

Official Title
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Cyclophosphamide-Busulfan Versus Busulfan-Cyclophosphamide as Conditioning Regimen Before Allogeneic Hematopoietic Stem Cell Transplantation for Leukemia: a Prospective Randomized Study to Assess Liver Toxicity

Conditions
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Myeloid Leukemia, Precursor Myeloid Neoplasms, Lymphoid Neoplasms

Intervention / Treatment
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* Drug: Busulfan-Cyclophosphamide as Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation
* Drug: Cyclophosphamide-Busulfan as Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BU-CY<br>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<br>* 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.<br>|
| Experimental: CY-BU<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver toxicity | Liver toxicity, assessed as absolute serum values of ASAT, ALAT, GGT, Alkaline Phosphatase, bilirubin at day 30. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VOD | Incidence and severity of veno occlusive disease (VOD) at day 30 | Day 30 | 
| Acute graft-versus-host disease (GvHD) | Incidence and severity of acute GVHD, by organ (skin, liver, gut) at day 30 and day 100 | Day 30 and Day 100 | 
| Toxicity | Organ toxicity at day 30 and day 100 | Day 30 and Day 100 | 
| Efficacy | Survival, relapse and non-relapse mortality at day 30 and day 100 | Day 30 and Day 100 | 
| Cumulative liver values | Cumulative serum values of aspartate transaminase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyltransferase (GGT), Alkaline Phosphatase, bilirubin for days 0, 10, 20 and 30 | Day 0, 10, 20 and 30 | 
| Maximum liver values | Maximum serum values of ASAT, ALAT, GGT, alkaline phosphatase (AP), bilirubin at any time between day 0 and day 30 | Day 0, 10, 20 and 30 |