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

Myelodysplastic Syndromes Clinical Trial

— FB-ATG  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00915811
• Other study ID #: 06CC12
• Secondary ID: REC - 06/Q0703/2
• Status: Terminated
• Phase: Phase 2
• First received: June 5, 2009
• Last updated: August 16, 2011
• Start date: June 2007
• Est. completion date: June 2011

Study information

• Verified date: June 2011
• Source: King's College Hospital NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Fludarabine
Fludarabine 30mg/m2 intravenously daily on days -9 to -5 inclusive of stem cell infusion.
• Busulphan
Busulphan 0.8mg/kg intravenously 6 hourly on days -4 and -3 of stem cell infusion.
• Thymoglobuline (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.

Procedure:
• Haematopoietic 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.

Locations

Country	Name	City	State
United Kingdom	King's College Hospital NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
King's College Hospital NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment related mortality to Day 100		Days 28, 56 and 100	Yes
Secondary	Incidence of single or multi-organ acute toxicity		Days 28, 56 and 100	Yes
Secondary	Incidence of graft failure/rejection		Days 28, 56 and 100	Yes
Secondary	Incidence of acute graft-versus-host disease		Days 28, 56, 100 and months 6, 9, 12, 18 and 24	Yes
Secondary	Incidence of systemic infections		Days 28, 56, 100 and months 6, 9, 12, 18 and 24	Yes
Secondary	EBV activation		Fortnightly for first 6 weeks after transplantation and then weekly for the first 6 months.	Yes
Secondary	Overall survival		Days 28, 56, 100 and months 6, 9, 12, 18 and 24	Yes
Secondary	Disease free survival/relapse risk		Days 28, 56, 100 and months 6, 9, 12, 18 and 24	Yes