Myelodysplastic SyndromesPhase 2FB-ATGNCT00915811
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
A Phase 2 study testing Fludarabine, Busulphan and Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme in people with Myelodysplastic Syndromes and Leukemia, Myeloid, Acute, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
- What is being tested?
- Fludarabine, Busulphan and Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2007to Jun 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 1. Related donors compatible for HLA-A, B, C, DRB1 and DQB1 by molecular typing.
Who cannot join
- 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
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- 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
- Donors who for any reason are unable to tolerate the leukapheresis procedure and cannot undergo anaesthesia for marrow harvest.
- Donors who are HIV-positive, or hepatitis B or C PCR positive.
- Donors who are medically unsuitable to donate
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
King's College Hospital NHS Foundation Trust
London, SE5 9RS
About this study
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
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.
- Being tested
- Fludarabine, Busulphan, Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme, Haematopoietic stem cell infusion
- Keywords
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Haematopoietic stem cell transplantation, Fludarabine, Busulphan, Thymoglobuline
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Fludarabine 30mg/m2 intravenously daily on days -9 to -5 inclusive of stem cell infusion.
BusulphanDrug
Busulphan 0.8mg/kg intravenously 6 hourly on days -4 and -3 of stem cell infusion.
Thymoglobuline (Anti-thymocyte globulin [rabbit]) - GenzymeDrug
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.
Haematopoietic stem cell infusionProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| FBATG | Experimental | Haematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline Receives: Drug: Fludarabine; Drug: Busulphan; Drug: Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme; Procedure: Haematopoietic stem cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment related mortality to Day 100
Measured: Days 28, 56 and 100
Secondary outcomes (7)
Incidence of single or multi-organ acute toxicity
Measured: Days 28, 56 and 100
Incidence of graft failure/rejection
Measured: Days 28, 56 and 100
Incidence of acute graft-versus-host disease
Measured: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Incidence of systemic infections
Measured: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
EBV activation
Measured: Fortnightly for first 6 weeks after transplantation and then weekly for the first 6 months.
Overall survival
Measured: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Disease free survival/relapse risk
Measured: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2009 (estimated)
- Study startJun 2007
- Primary completionJun 2011
- Study completionJun 2011
Why it stopped: FB ATG is now a standard for sib allo MDS patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Investigators
- Ghulam J Mufti, MB, DM, FRCP, FRCPath, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00915811
- Sponsor's protocol ID
- 06CC12
- Other IDs
- REC - 06/Q0703/208, EudraCT - 2006-004452-20
- Acronym
- FB-ATG
- Status last verified
- Jun 2011
- First submitted
- 5 Jun 2009
- Last updated
- 17 Aug 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00915811
- Acronym / sponsor ID
- FB-ATG / 06CC12
- Keywords
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Haematopoietic stem cell transplantation, Fludarabine, Busulphan, Thymoglobuline
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: FB ATG is now a standard for sib allo MDS patients
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 8 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FBATG | Experimental | Drug: Fludarabine, Drug: Busulphan, Drug: Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme, Procedure: Haematopoietic stem cell infusionHaematopoietic stem cell transplantation utilising conditioning with Fludarabine, Busulphan and Thymoglobuline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (18 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FludarabineFludarabine 30mg/m2 intravenously daily on days -9 to -5 inclusive of stem cell infusion. | Drug | FBATG |
| BusulphanBusulphan 0.8mg/kg intravenously 6 hourly on days -4 and -3 of stem cell infusion. | Drug | FBATG |
| Thymoglobuline (Anti-thymocyte globulin [rabbit]) - GenzymeThymoglobuline 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. | Drug | FBATG |
| Haematopoietic stem cell infusionThe 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. | Procedure or surgery | FBATG |
Primary outcome
Treatment related mortality to Day 100
Time frame: Days 28, 56 and 100
7 secondary outcomes
Incidence of single or multi-organ acute toxicity
Time frame: Days 28, 56 and 100
Incidence of graft failure/rejection
Time frame: Days 28, 56 and 100
Incidence of acute graft-versus-host disease
Time frame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Incidence of systemic infections
Time frame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
EBV activation
Time frame: Fortnightly for first 6 weeks after transplantation and then weekly for the first 6 months.
Overall survival
Time frame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Disease free survival/relapse risk
Time frame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24
Results and safety
The study was stopped early (reason given: FB ATG is now a standard for sib allo MDS patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ghulam J Mufti, MB, DM, FRCP, FRCPath principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludarabine, Busulphan and Thymoglobuline (Anti-thymocyte globulin [rabbit]) - Genzyme in people with Myelodysplastic Syndromes and Leukemia, Myeloid, Acute, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: FB ATG is now a standard for sib allo MDS patients). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment related mortality to Day 100 (time frame: Days 28, 56 and 100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2011.