Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT

March 1, 2018 updated by: University Hospital, Basel, Switzerland

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

72

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Basel, Switzerland, 4031
        • University Hospital, Basel
      • Geneva, Switzerland, 1205
        • University Hospital Geneva
      • Zurich, Switzerland, 8091
        • University Hospital Zurich

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liver toxicity
Time Frame: Day 30
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
Time Frame: Day 30
Incidence and severity of "veno occlusive disease (VOD)" at day 30
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
Day 30 and Day 100
Toxicity
Time Frame: Day 30 and Day 100
Organ toxicity at day 30 and day 100
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
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
Day 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
Day 0, 10, 20 and 30

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Day -8, 0, 10, 20 and 30
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.
Day -8, -3 and 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Basel, Switzerland

Collaborators

University Hospital, Geneva
University Hospital, Zürich

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

January 6, 2018

Study Completion (Actual)

January 6, 2018

Study Registration Dates

First Submitted

January 28, 2013

First Submitted That Met QC Criteria

January 28, 2013

First Posted (Estimate)

January 30, 2013

Study Record Updates

Last Update Posted (Actual)

March 2, 2018

Last Update Submitted That Met QC Criteria

March 1, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BuCyBu study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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