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

• Status: Terminated
• Trial end date: 2011-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: King's College Hospital NHS Trust
• Treatments: Antilymphocyte Serum; Busulfan; Fludarabine; Fludarabine phosphate; Thymoglobulin; Vidarabine

Criteria

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