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

A multi-centre phase II trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing thymoglobulin vs. calcineurin inhibitor or sirolimus-based post-transplant cyclophosphamide

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN50290131

Enrollment

400

Registered

2021-01-14

Start date

2021-02-22

Completion date

Unknown

Last updated

2025-09-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

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

Interventions

A prospective, multi-centre phase II randomised controlled study using a ‘pick a winner’ approach was chosen to compare two experimental arms to a control arm. The design is adaptive, using two interi

Eligibility

Sex/Gender

All

Inclusion criteria

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 _____ 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

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 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 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

Design outcomes

Primary

Measure	Time frame
GvHD-free, relapse-free survival at 1 year. GVHD assessment scoring will be performed as per the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria. GvHD-free, relapse-free survival (GRFS) defined as the time from date of day 0 (defined as the day of stem cell infusion) to the date of first event or death from any cause. An event is defined as GvHD (both acute and chronic), relapse or progression. Patients who are alive and event-free at the end of the trial will be censored at their date of last follow-up.	—

Measure

Time frame

GvHD-free, relapse-free survival at 1 year. GVHD assessment scoring will be performed as per the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria. GvHD-free, relapse-free survival (GRFS) defined as the time from date of day 0 (defined as the day of stem cell infusion) to the date of first event or death from any cause. An event is defined as GvHD (both acute and chronic), relapse or progression. Patients who are alive and event-free at the end of the trial will be censored at their date of last follow-up.

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Secondary

Measure	Time frame
1. Cumulative incidence of acute grade II-IV and III-IV GvHD measured using the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria at 1 year 2. Cumulative incidence of moderate and severe chronic GvHD measured using the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria at 1 year 3. Cumulative incidence of NRM at 1 year. Non-relapse mortality (NRM) is defined as the time from day 0 to date of non-relapse death. Patients who die post-relapse from any other cause will be considered a competing risk and patients alive at the end of the trial will be censored at their date last seen. 4. Overall survival at 1 year. Overall survival (OS) is defined as the time from day 0 to date of death, from any cause. Patients who are alive at the end of the trial will be censored at their date last seen. 5. Progression-free survival at 1 year. Progression-free survival (PFS) is defined as the time from day 0 to date of first relapse/progression or death from any cause. Patients who are alive and progression-free at the end of the trial will be censored at their date last seen. 6. Immune suppression-free survival at 1 year. Immune suppression-free survival is defined as the time from day 0 to the date of first immunosuppressive agent use. Patients who are alive and immune suppression free at the end of the trial will be censored at their date last seen. 7. Cumulative incidence of engraftment measured by blood sample at 1 year. Cumulative incidence of engraftment defined as the time from day 0 to date of engraftment (neutrophil engraftment defined to be the first of 3 consecutive days a neutrophil count =0.5 × 10^9/l is reached and platelet engraftment defined to be the first of 3 consecutive days an unsupported platelet count =20 × 10^9/l is reached). Patients who relapse/progress or die prior to relapse, progression or engraftment will be considered a competing risk at their date of rel	—

Measure

Time frame

1. Cumulative incidence of acute grade II-IV and III-IV GvHD measured using the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria at 1 year 2. Cumulative incidence of moderate and severe chronic GvHD measured using the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria at 1 year 3. Cumulative incidence of NRM at 1 year. Non-relapse mortality (NRM) is defined as the time from day 0 to date of non-relapse death. Patients who die post-relapse from any other cause will be considered a competing risk and patients alive at the end of the trial will be censored at their date last seen. 4. Overall survival at 1 year. Overall survival (OS) is defined as the time from day 0 to date of death, from any cause. Patients who are alive at the end of the trial will be censored at their date last seen. 5. Progression-free survival at 1 year. Progression-free survival (PFS) is defined as the time from day 0 to date of first relapse/progression or death from any cause. Patients who are alive and progression-free at the end of the trial will be censored at their date last seen. 6. Immune suppression-free survival at 1 year. Immune suppression-free survival is defined as the time from day 0 to the date of first immunosuppressive agent use. Patients who are alive and immune suppression free at the end of the trial will be censored at their date last seen. 7. Cumulative incidence of engraftment measured by blood sample at 1 year. Cumulative incidence of engraftment defined as the time from day 0 to date of engraftment (neutrophil engraftment defined to be the first of 3 consecutive days a neutrophil count =0.5 × 10^9/l is reached and platelet engraftment defined to be the first of 3 consecutive days an unsupported platelet count =20 × 10^9/l is reached). Patients who relapse/progress or die prior to relapse, progression or engraftment will be considered a competing risk at their date of rel

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Countries

England, Scotland, United Kingdom, Wales

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 5, 2026