Back to resultsPilot Study of Reduced Intensity Haematopoietic Stem Cell Transplantation in Patients With Poor Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukaemia (AML) Utilising Conditioning With Fludarabine, Busulphan and Thymoglobulin (FB-ATG)
Primary Purpose
Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Fludarabine
Busulphan
Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme
Haematopoietic stem cell infusion
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Haematopoietic stem cell transplantation, Fludarabine, Busulphan, Thymoglobuline
Eligibility Criteria
Inclusion Criteria:
Patient Selection
- Availability of a HLA compatible sibling donor
- Age >18 years
- Myelodysplastic Syndromes with IPSS Intermediate-2 or High.
- Poor risk acute myeloid leukaemia, de novo or transformed from MDS
- Ineligibility for standard conditioning allograft due to age or co-existing morbidities
Donor selection
1. Related donors compatible for HLA-A, B, C, DRB1 and DQB1 by molecular typing.
Exclusion Criteria:
Patient selection
- Cardiac insufficiency requiring treatment or symptomatic coronary artery disease.
- Hepatic disease, with AST > 2 times normal.
- Severe hypoxaemia, pO2 < 70 mm Hg, with decreased DLCO < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted.
- Impaired renal function (creatinine > 2 times upper limit of normal or creatinine clearance < 50% for age, gender, weight).
- Patients who have received previous treatment with Thymoglobuline
- HIV-positive patients.
- Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants.
- Life expectancy severely limited by diseases other than MDS or MPD.
- Serious concurrent untreated infection
- Patients with limited life expectancy for other reasons
- Serious psychiatric/ psychological disorders
- Absence of /inability to provide informed consent
Donor selection
- Age >75 years, unless independently assessed to be medically fit to donate
- Donors who for any reason are unable to tolerate the leukapheresis procedure and cannot undergo anaesthesia for marrow harvest.
- Donors who are HIV-positive, or hepatitis B or C PCR positive.
- Donors who are medically unsuitable to donate
Sites / Locations
- King's College Hospital NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
FBATG
Arm Description
Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline
Outcomes
Primary Outcome Measures
Treatment related mortality to Day 100
Secondary Outcome Measures
Incidence of single or multi-organ acute toxicity
Incidence of graft failure/rejection
Incidence of acute graft-versus-host disease
Incidence of systemic infections
EBV activation
Overall survival
Disease free survival/relapse risk
Full Information
NCT ID
NCT00915811
First Posted
June 5, 2009
Last Updated
August 16, 2011
Sponsor
King's College Hospital NHS Trust
1. Study Identification
Unique Protocol Identification Number
NCT00915811
Brief Title
Pilot Study of Reduced Intensity Haematopoietic Stem Cell Transplantation in Patients With Poor Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukaemia (AML) Utilising Conditioning With Fludarabine, Busulphan and Thymoglobulin
Acronym
FB-ATG
Official Title
Pilot Study of Reduced Intensity Haematopoietic Stem Cell Transplantation in Patients With Poor Risk Myelodysplastic Syndrome and Acute Myeloid Leukaemia Utilising Conditioning With Fludarabine, Busulphan and Thymoglobulin
Study Type
Interventional
2. Study Status
Record Verification Date
June 2011
Overall Recruitment Status
Terminated
Why Stopped
FB ATG is now a standard for sib allo MDS patients
Study Start Date
June 2007 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
King's College Hospital NHS Trust
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the safety and feasibility of conditioning with fludarabine, busulphan and thymoglobuline in patients with myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative disorders (MDS/MPD) or acute myeloid leukaemia (AML) undergoing haematopoietic stem cell allograft with granulocyte colony-stimulating factor (G-CSF)-mobilised peripheral blood stem cells (PBSC) (or bone marrow) from HLA compatible sibling donors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
Keywords
Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Haematopoietic stem cell transplantation, Fludarabine, Busulphan, Thymoglobuline
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
FBATG
Arm Type
Experimental
Arm Description
Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine 30mg/m2 intravenously daily on days -9 to -5 inclusive of stem cell infusion.
Intervention Type
Drug
Intervention Name(s)
Busulphan
Intervention Description
Busulphan 0.8mg/kg intravenously 6 hourly on days -4 and -3 of stem cell infusion.
Intervention Type
Drug
Intervention Name(s)
Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme
Intervention Description
Thymoglobuline will be given intravenously over a minimum of 6 hours for the first two doses and 4 hours for the subsequent doses. Acute side effects of ATG appear to be reduced if a very low dose is given for the first injection. Thymoglobuline 0.5mg/kg iv on day -4, 1.5mg/kg/day on day -3; and 2mg/kg/day iv on day -2 to -1 inclusive.
Intervention Type
Procedure
Intervention Name(s)
Haematopoietic stem cell infusion
Intervention Description
The source of stem cells will be PBSC wherever possible. Patients whose donors decline or are unable to donate PBSC will be transplanted with marrow cells.
Primary Outcome Measure Information:
Title
Treatment related mortality to Day 100
Time Frame
Days 28, 56 and 100
Secondary Outcome Measure Information:
Title
Incidence of single or multi-organ acute toxicity
Time Frame
Days 28, 56 and 100
Title
Incidence of graft failure/rejection
Time Frame
Days 28, 56 and 100
Title
Incidence of acute graft-versus-host disease
Time Frame
Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Title
Incidence of systemic infections
Time Frame
Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Title
EBV activation
Time Frame
Fortnightly for first 6 weeks after transplantation and then weekly for the first 6 months.
Title
Overall survival
Time Frame
Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Title
Disease free survival/relapse risk
Time Frame
Days 28, 56, 100 and months 6, 9, 12, 18 and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient Selection
Availability of a HLA compatible sibling donor
Age >18 years
Myelodysplastic Syndromes with IPSS Intermediate-2 or High.
Poor risk acute myeloid leukaemia, de novo or transformed from MDS
Ineligibility for standard conditioning allograft due to age or co-existing morbidities
Donor selection
1. Related donors compatible for HLA-A, B, C, DRB1 and DQB1 by molecular typing.
Exclusion Criteria:
Patient selection
Cardiac insufficiency requiring treatment or symptomatic coronary artery disease.
Hepatic disease, with AST > 2 times normal.
Severe hypoxaemia, pO2 < 70 mm Hg, with decreased DLCO < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted.
Impaired renal function (creatinine > 2 times upper limit of normal or creatinine clearance < 50% for age, gender, weight).
Patients who have received previous treatment with Thymoglobuline
HIV-positive patients.
Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants.
Life expectancy severely limited by diseases other than MDS or MPD.
Serious concurrent untreated infection
Patients with limited life expectancy for other reasons
Serious psychiatric/ psychological disorders
Absence of /inability to provide informed consent
Donor selection
Age >75 years, unless independently assessed to be medically fit to donate
Donors who for any reason are unable to tolerate the leukapheresis procedure and cannot undergo anaesthesia for marrow harvest.
Donors who are HIV-positive, or hepatitis B or C PCR positive.
Donors who are medically unsuitable to donate
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ghulam J Mufti, MB, DM, FRCP, FRCPath
Organizational Affiliation
King's College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
King's College Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Pilot Study of Reduced Intensity Haematopoietic Stem Cell Transplantation in Patients With Poor Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukaemia (AML) Utilising Conditioning With Fludarabine, Busulphan and Thymoglobulin
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