Comparing interventions for the prevention of graft-versus-host disease after unrelated donor stem cell transplantatio

Phase 2

• Conditions: 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; Cancer; Leukaemia, unspecified

• Registration Number: ISRCTN50290131
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-14
• Last Update Posted: 11 September 2023
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

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 commencing therapy until 12 months after transplant
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Previous inclusion criteria:
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 200mg/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)
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 commencing therapy until 12 months after transplant

Exclusion Criteria

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-defined
3. Known hypersensitivity to study drugs or history of hypersensitivity to rabbits
4. Pregnant or lactating women
5. Adults of reproductive potential not willing to use appropriate, highly effective, contraception during the specified period
6. Life expectancy <8 weeks
7. 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/min
8.3. 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
10. Contraindication to treatment with the study drugs (Thymoglobulin, cyclophosphamide, sirolimus, ciclosporin and mycophenolate mofetil) as detailed in each study drug SmPC
11. 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-defined
3. Known hypersensitivity to study drugs or history of hypersensitivity to rabbits
4. Pregnant or lactating women
5. Adults of reproductive potential not willing to use appropriate, highly effective, contraception during the specified period
6. Life expectancy <8 weeks
7. 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/min
8.3. 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified