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)

This study has been terminated.
(FB ATG is now a standard for sib allo MDS patients)
Sponsor:
Information provided by:
King's College Hospital NHS Trust
ClinicalTrials.gov Identifier:
NCT00915811
First received: June 5, 2009
Last updated: August 16, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndromes
Leukemia, Myeloid, Acute
Drug: Fludarabine
Drug: Busulphan
Drug: Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme
Procedure: Haematopoietic stem cell infusion
Phase 2

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

Resource links provided by NLM:


Further study details as provided by King's College Hospital NHS Trust:

Primary Outcome Measures:
  • Treatment related mortality to Day 100 [ Time Frame: Days 28, 56 and 100 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of single or multi-organ acute toxicity [ Time Frame: Days 28, 56 and 100 ] [ Designated as safety issue: Yes ]
  • Incidence of graft failure/rejection [ Time Frame: Days 28, 56 and 100 ] [ Designated as safety issue: Yes ]
  • Incidence of acute graft-versus-host disease [ Time Frame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24 ] [ Designated as safety issue: Yes ]
  • Incidence of systemic infections [ Time Frame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24 ] [ Designated as safety issue: Yes ]
  • EBV activation [ Time Frame: Fortnightly for first 6 weeks after transplantation and then weekly for the first 6 months. ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24 ] [ Designated as safety issue: Yes ]
  • Disease free survival/relapse risk [ Time Frame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: June 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FBATG
Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline
Drug: Fludarabine
Fludarabine 30mg/m2 intravenously daily on days -9 to -5 inclusive of stem cell infusion.
Drug: Busulphan
Busulphan 0.8mg/kg intravenously 6 hourly on days -4 and -3 of stem cell infusion.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00915811

Locations
United Kingdom
King's College Hospital NHS Foundation Trust
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
King's College Hospital NHS Trust
Investigators
Principal Investigator: Ghulam J Mufti, MB, DM, FRCP, FRCPath King's College London
  More Information

No publications provided

Responsible Party: Professor Ghulam Mufti, King's College London
ClinicalTrials.gov Identifier: NCT00915811     History of Changes
Other Study ID Numbers: 06CC12, REC - 06/Q0703/208, EudraCT - 2006-004452-20
Study First Received: June 5, 2009
Last Updated: August 16, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by King's College Hospital NHS Trust:
Myelodysplastic Syndromes
Leukemia, Myeloid, Acute
Haematopoietic stem cell transplantation
Fludarabine
Busulphan
Thymoglobuline

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Disease
Pathologic Processes
Fludarabine
Fludarabine phosphate
Busulfan
Antilymphocyte Serum
Vidarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Alkylating Agents

ClinicalTrials.gov processed this record on September 16, 2014