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 (FB-ATG)

King's College Hospital NHS Trust

Status and phase: Terminated; Phase 2

Conditions: Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Treatments: Drug: Fludarabine; Procedure: Haematopoietic stem cell infusion; Drug: Busulphan; Drug: Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme

Study type: Interventional

Funder types: Other

Identifiers

NCT00915811

REC - 06/Q0703/208

EudraCT - 2006-004452-20

06CC12

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

FBATG

Experimental group

Description:

Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline

Treatment:

Drug: Fludarabine

Procedure: Haematopoietic stem cell infusion

Drug: Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme

Drug: Busulphan