Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT

Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01779882
• Other study ID #: BuCyBu study
• Status: Completed
• Phase: N/A
• First received: January 28, 2013
• Last updated: March 1, 2018
• Start date: January 2013
• Est. completion date: January 6, 2018

Study information

• Verified date: March 2018
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: January 6, 2018
• Est. primary completion date: January 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Lymphoid Neoplasms
• Myeloid Leukemia
• Neoplasms
• Precursor Myeloid Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
Switzerland	University Hospital, Basel	Basel
Switzerland	University Hospital Geneva	Geneva
Switzerland	University Hospital Zurich	Zurich

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	University Hospital, Geneva, University Hospital, Zürich

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cytokines measurement	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.	Day -8, 0, 10, 20 and 30
Other	Pharmacogenomics	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.	Day -8, -3 and 0
Primary	Liver toxicity	Liver toxicity, assessed as absolute serum values of ASAT, ALAT, GGT, Alkaline Phosphatase, bilirubin at day 30.	Day 30
Secondary	VOD	Incidence and severity of "veno occlusive disease (VOD)" at day 30	Day 30
Secondary	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
Secondary	Toxicity	Organ toxicity at day 30 and day 100	Day 30 and Day 100
Secondary	Efficacy	Survival, relapse and non-relapse mortality at day 30 and day 100	Day 30 and Day 100
Secondary	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
Secondary	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