Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT

This study is currently recruiting participants.

Verified January 2013 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: NA

Last verified: January 2013

History: No changes posted

Tracking Information

First Received Date ^ICMJE

January 28, 2013

Last Updated Date

January 28, 2013

Start Date ^ICMJE

January 2013

Estimated Primary Completion Date

June 2015 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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.

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

No Changes Posted

Current Secondary Outcome Measures ^ICMJE

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

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

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.

Original Other Outcome Measures ^ICMJE

Same as current

Descriptive Information

Brief Title ^ICMJE

Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT

Official Title ^ICMJE

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

Brief 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.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Not Provided

Study Design ^ICMJE

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Myeloid Leukemia
Precursor Myeloid Neoplasms
Lymphoid Neoplasms

Intervention ^ICMJE

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.

Study Arm (s)

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

Publications *

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.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Completion Date

Not Provided

Estimated Primary Completion Date

June 2015 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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-/NK-cell neoplasms).
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 > 3xULN 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

Gender

Both

Ages

18 Years to 65 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

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

Location Countries ^ICMJE

Switzerland

Administrative Information

NCT Number ^ICMJE

NCT01779882

Other Study ID Numbers ^ICMJE

BuCyBu study

Has Data Monitoring Committee

Responsible Party

University Hospital, Basel, Switzerland

Study Sponsor ^ICMJE

University Hospital, Basel, Switzerland

Collaborators ^ICMJE

University Hospital, Zürich
University Hospital, Geneva

Investigators ^ICMJE

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

Information Provided By

University Hospital, Basel, Switzerland

Verification Date

January 2013

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

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