Clinical trial NCT00915811: 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
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Leukemia, Myeloid, Acute
Keywords: Myelodysplastic Syndromes
Leukemia, Myeloid, Acute
Haematopoietic stem cell transplantation
Fludarabine
Busulphan
Thymoglobuline
Lead sponsor: King's College Hospital NHS Trust
Sponsor class: OTHER
First posted: 2009-06-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Treatment related mortality to Day 100
timeFrame: Days 28, 56 and 100
Secondary outcomes:
measure: Incidence of single or multi-organ acute toxicity
timeFrame: Days 28, 56 and 100
measure: Incidence of graft failure/rejection
timeFrame: Days 28, 56 and 100
measure: Incidence of acute graft-versus-host disease
timeFrame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
measure: Incidence of systemic infections
timeFrame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
measure: EBV activation
timeFrame: Fortnightly for first 6 weeks after transplantation and then weekly for the first 6 months.
measure: Overall survival
timeFrame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
measure: Disease free survival/relapse risk
timeFrame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
Study officials:
affiliation: King's College London
name: Ghulam J Mufti, MB, DM, FRCP, FRCPath
role: PRINCIPAL_INVESTIGATOR
References: