Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University Hospital, Basel, Switzerland
Sponsor:
Collaborators:
University Hospital, Zürich
University Hospital, Geneva
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT01779882
First received: January 28, 2013
Last updated: August 19, 2014
Last verified: August 2014

January 28, 2013
August 19, 2014
January 2013
June 2015   (final data collection date for primary outcome measure)
Liver toxicity [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
Liver toxicity, assessed as absolute serum values of ASAT, ALAT, GGT, Alkaline Phosphatase, bilirubin at day 30.
Same as current
Complete list of historical versions of study NCT01779882 on ClinicalTrials.gov Archive Site
  • VOD [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
    Incidence and severity of "veno occlusive disease (VOD)" at day 30
  • Acute graft-versus-host disease (GvHD) [ Time Frame: Day 30 and Day 100 ] [ Designated as safety issue: No ]
    Incidence and severity of acute GVHD, by organ (skin, liver, gut) at day 30 and day 100
  • Toxicity [ Time Frame: Day 30 and Day 100 ] [ Designated as safety issue: Yes ]
    Organ toxicity at day 30 and day 100
  • Efficacy [ Time Frame: Day 30 and Day 100 ] [ Designated as safety issue: No ]
    Survival, relapse and non-relapse mortality at day 30 and day 100
  • Cumulative liver values [ Time Frame: Day 0, 10, 20 and 30 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 0, 10, 20 and 30 ] [ Designated as safety issue: Yes ]
    Maximum serum values of ASAT, ALAT, GGT, alkaline phosphatase (AP), bilirubin at any time between day 0 and day 30
  • VOD [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
    Incidence and severity of "veno occlusive disease (VOD)" at day 30
  • Acute graft-versus-host disease (GvHD) [ Time Frame: Day 30 and Day 100 ] [ Designated as safety issue: No ]
    Incidence and severity of acute GVHD, by organ (skin, liver, gut) at day 30 and day 100
  • Toxicity [ Time Frame: Day 30 and Day 100 ] [ Designated as safety issue: Yes ]
    Organ toxicity at day 30 and day 100
  • Efficacy [ Time Frame: Day 30 and Day 100 ] [ Designated as safety issue: No ]
    Survival, relapse and non-relapse mortality at day 30 and day 100
  • Cumulative liver values [ Time Frame: Day 0, 10, 20 and 30 ] [ Designated as safety issue: Yes ]
    Cumulative serum values of ASAT, ALAT, GGT, Alkaline Phosphatase, bilirubin for days 0, 10, 20 and 30
  • Maximum liver values [ Time Frame: Day 0, 10, 20 and 30 ] [ Designated as safety issue: Yes ]
    Maximum serum values of ASAT, ALAT, GGT, AP, bilirubin at any time between day 0 and day 30
  • Cytokines measurement [ Time Frame: Day -8, 0, 10, 20 and 30 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day -8, -3 and 0 ] [ Designated as safety issue: No ]
    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.
Same as current
 
Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT
Cyclophosphamide-Busulfan Versus Busulfan-Cyclophosphamide as Conditioning Regimen Before Allogeneic Hematopoietic Stem Cell Transplantation for Leukemia: a Prospective Randomized Study to Assess Liver Toxicity

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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Myeloid Leukemia
  • Precursor Myeloid Neoplasms
  • Lymphoid Neoplasms
  • 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.
  • 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.
  • Active Comparator: BU-CY
    Group A (standard group): conditioning regimen with Busulfan (BU) followed by Cyclophosphamide (CY)
    Intervention: Drug: Busulfan-Cyclophosphamide as Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation
  • Experimental: CY-BU
    Group B (experimental group): conditioning regimen with Cyclophosphamide (CY) followed by Busulfan (BU)
    Intervention: Drug: Cyclophosphamide-Busulfan as Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
65
Not Provided
June 2015   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact: Nathan Cantoni, MD +41628389844 nathan.cantoni@ksa.ch
Contact: Sabine Gerull, MD +41613287683 sabine.gerull@usb.ch
Switzerland
 
NCT01779882
BuCyBu study
No
University Hospital, Basel, Switzerland
University Hospital, Basel, Switzerland
  • University Hospital, Zürich
  • University Hospital, Geneva
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
University Hospital, Basel, Switzerland
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP