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

Phase 2

Terminated

• Conditions: Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
• Interventions: Drug: Fludarabine; Drug: Busulphan; Drug: Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme; Procedure: Haematopoietic stem cell infusion

• Registration Number: NCT00915811
• Lead Sponsor: King's College Hospital NHS Trust

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-06
• Study First Submitted: 2009-06-05
• Study First Submitted QC: 2009-06-05
• Study First Posted: 2009-06-08
• Status Verified: 2011-06
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Last Update Submitted: 2011-08-16
• Last Update Posted: 2011-08-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FBATG	Fludarabine	Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline
FBATG	Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme	Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline
FBATG	Haematopoietic stem cell infusion	Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline
FBATG	Busulphan	Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline

Primary Outcome Measures

Name	Time	Method
Treatment related mortality to Day 100	Days 28, 56 and 100

Secondary Outcome Measures

Name	Time	Method
Incidence of single or multi-organ acute toxicity	Days 28, 56 and 100
Disease free survival/relapse risk	Days 28, 56, 100 and months 6, 9, 12, 18 and 24
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

Trial Locations

Locations (1)

King's College Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom