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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Prof
Ronjon
Chakraverty
+44 (0)2077940500
ronjon.chakraverty@ndcls.ox.ac.uk
Dr
Andrea
Hodgkinson
+44 (0)121 371 4365
a.hodgkinson@bham.ac.uk
Acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myelomonocytic leukemia (CMML), myelodysplastic syndromes (MDS), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma (MM), chronic lymphocytic leukaemia (CLL), chronic myeloid leukaemia (CML), myelofibrosis
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Stem cell transplantation from a donor (called ‘allogeneic transplant’) is the only curative therapy for many children and adults with blood cancer. One of the main complications after a transplant is a condition called graft versus host disease (GvHD) which occurs when donor cells (the ‘graft’) see the patient’s (the ‘host’s) normal cells (such as healthy skin, gut or liver) as ‘different’ and attacks them. This can be beneficial as it means that the new immune system is working and is likely to be attacking any remaining or returning disease. This is referred to as ‘graft versus leukaemia’ or ‘graft-versus-tumour’ effect. However, too much GvHD can cause unwanted complications and side effects, including damage to the liver, eyes, mouth, gut, lungs or skin.
Patients currently receive a combination of drugs and antibodies during and after their transplant to prevent GvHD. A number of new approaches have been developed to prevent GvHD from occurring, some of which will be looked at in this trial.
This is a late phase trial composed of three parts (randomisations) which will compare three different treatments:
1. One of the standard UK and European approaches for GvHD prevention using the drugs thymoglobulin, cyclosporine and mycophenolate mofetil (called MMF for short)
2. A new approach using the drugs cyclophosphamide, MMF and cyclosporine
3. A new approach using the drugs cyclophosphamide, MMF and sirolimus
Although there is good evidence from a number of previous studies that the newer approaches may be beneficial in reducing the risk of GvHD compared to other treatment approaches, these have not been compared with the standard approach in the UK. The aim of this trial is to see if the use of these new approaches is better at preventing GvHD occurring compared to the standard approach.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
2025 Protocol article in https://pubmed.ncbi.nlm.nih.gov/39880444/ (added 30/01/2025)
You can take part if:
Current inclusion criteria as of 29/08/2023:
1. Availability of suitably matched unrelated donor (9/10 or 10/10)
2. Planned to receive one of the following reduced-intensity conditioning (RIC) protocols:
2.1. Fludarabine-melphalan (fludarabine 120-180 mg/m²; melphalan ≤150 mg/m²)
2.2. BEAM or LEAM (carmustine 300 mg/m² or lomustine 200 mg/m² with: etoposide 800 mg/m²; cytarabine 1600 mg/m²; melphalan 140 mg/m²)
2.3. Fludarabine-busulphan (fludarabine 120-180 mg/m²; busulphan ≤8 mg/kg PO or 6.4 mg/kg IV)
2.4. Fludarabine-treosulfan (fludarabine 150 mg/m² IV; treosulfan 30 g/m² IV)
3. Planned use of peripheral blood stem cells (PBSCs) for transplantation
4. Planned allo-SCT for one of the following haematological malignancies:
4.1. AML in complete remission (CR)
4.2. ALL in CR
4.3. CMML <10% blasts
4.4. MDS <10% blasts
4.5. NHL in CR/partial remission (PR)
4.6. HL in CR/PR
4.7. MM in CR/PR
4.8. CLL in CR/PR
4.9. CML in 1st or 2nd chronic phase
4.10. Myelofibrosis
5. Age 16-70 years
6. Females of and male patients of reproductive potential (i.e., not post-menopausal or surgically sterilised) must agree to use appropriate, highly effective, contraception from the point of
You may not be able to take part if:
Current exclusion criteria as of 29/08/2023:1. Use of any method of graft manipulation (excluding storage of future donor lymphocyte infusion)2. Use of alemtuzumab or any method of T-cell depletion except those that are protocol-defined3. Known hypersensitivity to study drugs or history of hypersensitivity to rabbits4. Pregnant or lactating women5. Adults of reproductive potential not willing to use appropriate, highly effective, contraception during the specified period6. Life expectancy <8 weeks7. Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection 8. Organ dysfunction defined as:8.1. Left ventricular ejection fraction (LVEF) <45%8.2. Glomerular filtration rate (GFR) <50 ml/min8.3. Bilirubin >50 µmol/l 8.4. Aspartate transaminase (AST) or alanine transferase (ALT) >3 x upper limit of normal (ULN)9. Participation in COSI or ALL-RIC trials10. Contraindication to treatment with the study drugs (Thymoglobulin, cyclophosphamide, sirolimus, ciclosporin and mycophenolate mofetil) as detailed in each study drug SmPC11. Patient has any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory, cardiovascular) or significant disorder which, in the opinion of the investigator would jeopardise the safety of the patient by taking part in the trial
_____
Previous exclusion criteria:1. Use of any method of graft manipulation (excluding storage of future donor lymphocyte infusion)2. Use of alemtuzumab or any method of T-cell depletion except those that are protocol-defined3. Known hypersensitivity to study drugs or history of hypersensitivity to rabbits4. Pregnant or lactating women5. Adults of reproductive potential not willing to use appropriate, highly effective, contraception during the specified period6. Life expectancy <8 weeks7. Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection 8. Organ dysfunction defined as:8.1. Left ventricular ejection fraction (LVEF) <45%8.2. Glomerular filtration rate (GFR) <50 ml/min8.3. Bilirubin >50 µmol/l 8.4. Aspartate transaminase (AST) or alanine transferase (ALT) >3 x upper limit of normal (ULN)9. Participation in COSI or ALL-RIC trials
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Prof
Ronjon
Chakraverty
+44 (0)2077940500
ronjon.chakraverty@ndcls.ox.ac.uk
Dr
Andrea
Hodgkinson
+44 (0)121 371 4365
a.hodgkinson@bham.ac.uk
The study is sponsored by University of Birmingham and funded by Leukaemia UK.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Or CPMS 46327
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