Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
Conditions
Keywords
Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Haematopoietic stem cell transplantation, Fludarabine, Busulphan, Thymoglobuline
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.
Interventions
DRUGFludarabine
Fludarabine 30mg/m2 intravenously daily on days -9 to -5 inclusive of stem cell infusion.
DRUGBusulphan
Busulphan 0.8mg/kg intravenously 6 hourly on days -4 and -3 of stem cell infusion.
DRUGThymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme
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.
PROCEDUREHaematopoietic stem cell infusion
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.
Sponsors
King's College Hospital NHS Trust
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patient Selection 1. Availability of a HLA compatible sibling donor 2. Age \>18 years 3. Myelodysplastic Syndromes with IPSS Intermediate-2 or High. 4. Poor risk acute myeloid leukaemia, de novo or transformed from MDS 5. 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 1. Cardiac insufficiency requiring treatment or symptomatic coronary artery disease. 2. Hepatic disease, with AST \> 2 times normal. 3. 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. 4. Impaired renal function (creatinine \> 2 times upper limit of normal or creatinine clearance \< 50% for age, gender, weight). 5. Patients who have received previous treatment with Thymoglobuline 6. HIV-positive patients. 7. Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants. 8. Life expectancy severely limited by diseases other than MDS or MPD. 9. Serious concurrent untreated infection 10. Patients with limited life expectancy for other reasons 11. Serious psychiatric/ psychological disorders 12. Absence of /inability to provide informed consent Donor selection 1. Age \>75 years, unless independently assessed to be medically fit to donate 2. Donors who for any reason are unable to tolerate the leukapheresis procedure and cannot undergo anaesthesia for marrow harvest. 3. Donors who are HIV-positive, or hepatitis B or C PCR positive. 4. Donors who are medically unsuitable to donate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment related mortality to Day 100 | Days 28, 56 and 100 |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of single or multi-organ acute toxicity | Days 28, 56 and 100 |
| Incidence of graft failure/rejection | Days 28, 56 and 100 |
| Incidence of acute graft-versus-host disease | Days 28, 56, 100 and months 6, 9, 12, 18 and 24 |
| Incidence of systemic infections | Days 28, 56, 100 and months 6, 9, 12, 18 and 24 |
| EBV activation | Fortnightly for first 6 weeks after transplantation and then weekly for the first 6 months. |
| Overall survival | Days 28, 56, 100 and months 6, 9, 12, 18 and 24 |
| Disease free survival/relapse risk | Days 28, 56, 100 and months 6, 9, 12, 18 and 24 |
Countries
United Kingdom
Outcome results
None listed