Cyclophosphamide and Busulfan as Conditioning Regimen Before Allogeneic HSCT - Full Text View

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 Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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:

MedlinePlus related topics: Cancer Leukemia

Drug Information available for: Cyclophosphamide Busulfan

U.S. FDA Resources

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

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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

Other Outcome Measures:

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.

Estimated Enrollment:	65
Study Start Date:	January 2013
Estimated Primary Completion Date:	June 2015 (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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
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-/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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: 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	Not yet recruiting
Geneva, Switzerland, 1205
Principal Investigator: Yves Chalandon, MD
University Hospital Zurich	Not yet 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:

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.

Responsible Party:	University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:	NCT01779882 History of Changes
Other Study ID Numbers:	BuCyBu study
Study First Received:	January 28, 2013
Last Updated:	January 28, 2013
Health Authority:	Switzerland: Ethikkommission Switzerland: Swissmedic

Additional relevant MeSH terms:

Neoplasms
Leukemia
Leukemia, Myeloid
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Busulfan
Cyclophosphamide

Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 21, 2013