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

NCT00915811 | Terminated Phase 2

• 3 other identifiers: 06CC12REC - 06/Q0703/208EudraCT - 2006-004452-20
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Keywords

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Haematopoietic stem cell transplantation; Fludarabine; Busulphan; Thymoglobuline

Outcome Measures

Primary Outcomes (1)

• Treatment related mortality to Day 100

  Days 28, 56 and 100

Secondary Outcomes (7)

• Incidence of single or multi-organ acute toxicity

  Days 28, 56 and 100

• 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.

Study Arms (1)

FBATG

EXPERIMENTAL

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

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

Interventions

Fludarabine DRUG

Fludarabine 30mg/m2 intravenously daily on days -9 to -5 inclusive of stem cell infusion.

FBATG

Busulphan DRUG

Busulphan 0.8mg/kg intravenously 6 hourly on days -4 and -3 of stem cell infusion.

FBATG

Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme DRUG

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.

FBATG

Haematopoietic stem cell infusion PROCEDURE

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.

FBATG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient Selection
• Availability of a HLA compatible sibling donor
• Age \>18 years
• Myelodysplastic Syndromes with IPSS Intermediate-2 or High.
• Poor risk acute myeloid leukaemia, de novo or transformed from MDS
• Ineligibility for standard conditioning allograft due to age or co-existing morbidities
• Donor selection
• \. Related donors compatible for HLA-A, B, C, DRB1 and DQB1 by molecular typing.

You may not qualify if:

• Patient selection
• Cardiac insufficiency requiring treatment or symptomatic coronary artery disease.
• Hepatic disease, with AST \> 2 times normal.
• 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.
• Impaired renal function (creatinine \> 2 times upper limit of normal or creatinine clearance \< 50% for age, gender, weight).
• Patients who have received previous treatment with Thymoglobuline
• HIV-positive patients.
• Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants.
• Life expectancy severely limited by diseases other than MDS or MPD.
• Serious concurrent untreated infection
• Patients with limited life expectancy for other reasons
• Serious psychiatric/ psychological disorders
• Absence of /inability to provide informed consent
• Donor selection
• Age \>75 years, unless independently assessed to be medically fit to donate

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead

Study Sites (1)

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

fludarabine; Busulfan; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Ghulam J Mufti, MB, DM, FRCP, FRCPath

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 5, 2009
• First Posted: June 8, 2009
• Study Start: June 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: August 17, 2011

Record last verified: 2011-06

Locations

GB (1)