MoTD: 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
Study design/summary: This is a prospective, phase II, multicentre, randomised clinical trial in patients undergoing reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). The trial will compare the novel graft-versus-host disease (GVHD) prophylaxis regimens post-transplant cyclophosphamide (PTCy)-Calcineurin inhibitor (CNI) (PTCy-CNI) or PTCy-Sirolimus to a current standard-of-care involving the use of T-cell depletion with Thymoglobulin. Patients will be stratified at randomisation by their randomising centre, disease risk score and Human leukocyte antigen (HLA) match (10/10 or 9/10). Patients eligible for entry into the trial will be randomised on a 1:1:1 ratio to receive either one of the experimental treatment arms or the control arm.
- The primary objective is to evaluate the percentage 1-year GVHD-free, relapse-free Survival (GRFS).
- The secondary objectives are to evaluate the cumulative incidence of acute GVHD, the cumulative incidence chronic GVHD (cGVHD), the cumulative incidence of non-relapse mortality (NRM), immune suppression-free survival, overall survival (OS), progression free survival (PFS), GRFS, engraftment, chimerism, incidence of infection requiring inpatient admission, the number of inpatient days, the timing and dose of donor lymphocyte infusion (DLI), rituximab use/incidence of Epstein-Barr virus (EBV) re-activation-post transplant lymphoproliferative disease (PTLD), quality of life (QoL), proportion of patients with hemorrhagic cystitis, proportion of patients cytomegalovirus (CMV) viremia and CMV end-organ disease, and proportion of patients who received 2nd line therapies for treatment of acute GVHD.
Centres: 22 IMPACT centres
Target Number of patients: 400 patients will be randomised to the MoTD trial across IMPACT centres.
Patient population: Adults considered suitable for an allo-SCT with the following haematological malignancies will be recruited to this trial:
- 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)
Sponsorship/Funding: University of Birmingham, funded by the IMPACT network
Trial Status: In set-up.
Start Date: TBC
Duration: 5 years. Patients will be recruited over 48 months. Patients will be followed up for a minimum of 1 year.
Trial Contacts: TBC
If you are a patient and interested in taking part in a clinical trial, please speak with your consultant who will be able to offer you further information and discuss whether it is suitable for you. A referral from your medical team would be required in order to consider you for treatment on a clinical trial.