RATinG (Risk Adapted Therapy in acute GvHD): investigating the use of lenzilumab for treating high-risk acute graft versus host disease following allogeneic stem cell transplantation
Graft versus host disease following allogeneic stem cell transplantation
RATinG is a multicentre trial in the UK in patients with acute Graft versus Host Disease (aGvHD) following allogeneic stem cell transplantation. It is a double-blind, randomised (1:1) controlled trial. The study comprises of two stages; Stage 1 of the study will recruit high-risk biomarker patients to a safety cohort treated with lenzilumab. In stage 2 of the study, patients with a high-risk biomarker category will be randomised to receive lenzilumab or placebo for 14 weeks or until GvHD progression, and low-risk patients will be recruited into an observational cohort. The primary outcome of the study is to assess the safety of lenzilumab in the safety cohort and to evaluate non-relapse mortality, which is defined as the time to death without relapse or recurrence, in the treatment arms. The treatment arms will be compared in terms of toxicity (side effects), the rate of acute and chronic GvHD, overall survival, time to treatment failure, quality of life, steroid exposure, time to response or disease progression. Lenzilumab has been evaluated to date in studies of COVID19, asthma and rheumatoid arthritis. This will be the first study of lenzilumab in a haematological disease, but studies to date have shown that the drug is well tolerated. In stage 1 of the study, 20 patients will be recruited to a single-arm cohort treated with lenzilumab. Following this, in stage 2 of the study, a minimum of 220 patients with biomarker defined high-risk acute GvHD following allogeneic stem cell transplantation (SCT) will be randomised to receive treatment of either lenzilumab or placebo. Any patients who do not meet the criteria of being high risk will be recruited into an observational cohort of the study. Interim Analysis There are two interim analyses in this trial, one at the end of stage 1 of the trial and the other during stage 2 of the trial. The first interim analysis will be conducted once all 20 patients have been recruited to stage 1 of the trial and have completed 6 we
Stage 1 and Stage 2 - Randomised Cohort: 1. Aged ≥16 years 2. Recipient of allogeneic stem cell transplant 3. Acute graft versus host disease (aGvHD) (grade I-IV) requiring treatment with systemic steroids (PO prednisolone or IV methylprednisolone equivalent to prednisolone dose of ≥1 mg/kg) 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-3 (see Appendix 2) 5. High-risk patients with an Ann Arbor high or intermediate risk score (Appendix 3) Stage 2 - Observational Cohort: 1. Aged ≥16 years 2. Recipient of allogeneic stem cell transplant 3. aGvHD (grade I-IV) requiring treatment with systemic steroids (PO prednisolone or IV methylprednisolone equivalent to prednisolone dose of ≥1 mg/kg) 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-3 (see Appendix 2) 5. Low risk patients with Ann Arbor low risk score (Appendix 3)
All Cohorts: 1. Any additional treatment for GvHD excluding continuance of current prophylaxis or re-institution of drugs previously used for prophylaxis 2. Patients requiring treatment with topical steroids only 3. Known HIV or active hepatitis B/C (currently receiving treatment) 4. Patients treated with >4 days of steroids for aGvHD (maximum of 20 mg for other indications) 5. Female patients who are pregnant or breastfeeding. All women of childbearing potential must have a negative pregnancy test before registration/randomisation Stage 1 and Stage 2 - Randomised Cohort: 1. Adults of reproductive potential not willing to use appropriate, highly effective, contraception during the specified period