Investigating the use of lenzilumab for acute graft versus host disease (when transplanted stem cells attack the body’s cells)

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

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN42585840

Enrollment

590

Registered

2022-02-08

Start date

2022-01-01

Completion date

Unknown

Last updated

2026-07-13

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

Conditions

Graft versus host disease following allogeneic stem cell transplantation Injury, Occupational Diseases, Poisoning

Interventions

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

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 r

Eligibility

Sex/Gender

All

Age

16 Years to 100 Years

Inclusion criteria

Inclusion criteria: 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)

Exclusion criteria

Exclusion criteria: 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

Design outcomes

Primary

Measure	Time frame
Stage 1: reported whilst on treatment and up to 6 months following completion/discontinuation: 1. The primary outcome measure of safety is defined to be the number of patients who experience one or more of the following events: 1.1. Invasive fungal infections (IFI): the threshold for continuation to the randomised stage of the trial is the observation of four cases of proven or probable IFI 1.2. Mycobacterial infection (MBI): the threshold for non-continuation to the randomised stage of the trial is the observation of a single case of MBI 1.3. Pulmonary alveolar proteinosis (PAP): the threshold for non-continuation to the randomised stage of the trial is the observation of a single case of PAP, confirmed by radiology and bronchoscopy 1.4. Other adverse events (AEs): no threshold for adverse events other than those defined above are proposed Stage 2: Time to non-relapse mortality (NRM), defined as the time from date of randomisation to date of death without relapse. Patients who relapse from their underlying disease will be considered a competing risk at their date of relapse. Patients who are alive and relapse-free at the end of the trial will be censored at their date last seen.	—

Measure

Time frame

Stage 1: reported whilst on treatment and up to 6 months following completion/discontinuation: 1. The primary outcome measure of safety is defined to be the number of patients who experience one or more of the following events: 1.1. Invasive fungal infections (IFI): the threshold for continuation to the randomised stage of the trial is the observation of four cases of proven or probable IFI 1.2. Mycobacterial infection (MBI): the threshold for non-continuation to the randomised stage of the trial is the observation of a single case of MBI 1.3. Pulmonary alveolar proteinosis (PAP): the threshold for non-continuation to the randomised stage of the trial is the observation of a single case of PAP, confirmed by radiology and bronchoscopy 1.4. Other adverse events (AEs): no threshold for adverse events other than those defined above are proposed Stage 2: Time to non-relapse mortality (NRM), defined as the time from date of randomisation to date of death without relapse. Patients who relapse from their underlying disease will be considered a competing risk at their date of relapse. Patients who are alive and relapse-free at the end of the trial will be censored at their date last seen.

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Secondary

Measure	Time frame
Stage 1: 1. Overall aGvHD response rate (complete and partial response) at day 28 from the start of trial treatment, response defined as per the REACH-2 trial as the proportion of patients with complete or partial response: 1.1. Complete response - score of 0 for aGvHD grading in all evaluable organs, indicating complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response, or non-response of aGvHD 1.2. Partial response - improvement of 1 stage in one or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response, or non-response of aGvHD 2. Feasibility of recruitment to the randomised stage of the trial, defined as the proportion of patients screened that were high risk and length of recruitment. For the randomised element of the trial to be deemed feasible at least 40% of the patients screened for stage 1 will have to be categorised as high risk (AA2/3) GvHD patients and despite there being no defined threshold for either time to recruitment completion or laboratory turnaround time both will be reviewed as part of the feasibility assessment. Measured after completion of stage 1 recruitment (risk category assigned and the patient receives the first dose). Stage 2: 1. Overall aGvHD response rate (complete and partial response) at day 28 from the start of trial treatment, response defined as per the REACH-2 trial as the proportion of patients with complete or partial response: 1.1. Complete response - score of 0 for aGvHD grading in all evaluable organs, indicating complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response, or non-response of aGvHD 1.2. Partial response - improvement of 1 stage in one	—

Measure

Time frame

Stage 1: 1. Overall aGvHD response rate (complete and partial response) at day 28 from the start of trial treatment, response defined as per the REACH-2 trial as the proportion of patients with complete or partial response: 1.1. Complete response - score of 0 for aGvHD grading in all evaluable organs, indicating complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response, or non-response of aGvHD 1.2. Partial response - improvement of 1 stage in one or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response, or non-response of aGvHD 2. Feasibility of recruitment to the randomised stage of the trial, defined as the proportion of patients screened that were high risk and length of recruitment. For the randomised element of the trial to be deemed feasible at least 40% of the patients screened for stage 1 will have to be categorised as high risk (AA2/3) GvHD patients and despite there being no defined threshold for either time to recruitment completion or laboratory turnaround time both will be reviewed as part of the feasibility assessment. Measured after completion of stage 1 recruitment (risk category assigned and the patient receives the first dose). Stage 2: 1. Overall aGvHD response rate (complete and partial response) at day 28 from the start of trial treatment, response defined as per the REACH-2 trial as the proportion of patients with complete or partial response: 1.1. Complete response - score of 0 for aGvHD grading in all evaluable organs, indicating complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response, or non-response of aGvHD 1.2. Partial response - improvement of 1 stage in one

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Countries

England, Scotland, United Kingdom, Wales

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Jul 23, 2026