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Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT

This study is currently recruiting participants.
Verified August 2017 by University Hospital, Basel, Switzerland
Sponsor:
ClinicalTrials.gov Identifier:
NCT01779882
First Posted: January 30, 2013
Last Update Posted: August 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
University Hospital, Zürich
University Hospital, Geneva
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
  Purpose
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 Intervention
Myeloid Leukemia Precursor Myeloid Neoplasms Lymphoid Neoplasms Drug: Busulfan-Cyclophosphamide as Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation Drug: Cyclophosphamide-Busulfan as Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation

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

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Liver toxicity [ Time Frame: Day 30 ]
    Liver toxicity, assessed as absolute serum values of ASAT, ALAT, GGT, Alkaline Phosphatase, bilirubin at day 30.


Secondary Outcome Measures:
  • VOD [ Time Frame: Day 30 ]
    Incidence and severity of "veno occlusive disease (VOD)" at day 30

  • Acute graft-versus-host disease (GvHD) [ Time Frame: Day 30 and Day 100 ]
    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 ]
    Organ toxicity at day 30 and day 100

  • Efficacy [ Time Frame: Day 30 and Day 100 ]
    Survival, relapse and non-relapse mortality at day 30 and day 100

  • Cumulative liver values [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.


Estimated Enrollment: 65
Study Start Date: January 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01779882


Contacts
Contact: Nathan Cantoni, MD +41628389844 nathan.cantoni@ksa.ch
Contact: Sabine Gerull, MD +41613287683 sabine.gerull@usb.ch

Locations
Switzerland
University Hospital, Basel Recruiting
Basel, Switzerland, 4031
Principal Investigator: Sabine Gerull, MD         
Sub-Investigator: Jakob Passweg, MD         
University Hospital Geneva Recruiting
Geneva, Switzerland, 1205
Contact: Yves Chalandon, MD         
Principal Investigator: Yves Chalandon, MD         
University Hospital Zurich Recruiting
Zurich, Switzerland, 8091
Contact: Gayathri Nair, MD    +41442551111    gayathri.nair@usz.ch   
Principal Investigator: Gayathri Nair, MD         
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
  More Information

Publications:
Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT01779882     History of Changes
Other Study ID Numbers: BuCyBu study
First Submitted: January 28, 2013
First Posted: January 30, 2013
Last Update Posted: August 3, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Leukemia
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Busulfan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists