ANIMATE: Phase II Study of Nivolumab Monotherapy for Relapsed/Refractory Hodgkin Lymphoma
- Registration Number
- NCT03337919
- Lead Sponsor
- University College, London
- Brief Summary
This is a single-arm, phase II, multi-centre study of the safety and efficacy of the PD-1 inhibitor, nivolumab, as second-line or third-line salvage therapy as a bridge to stem cell transplant (SCT) in relapsed/ refractory classical Hodgkin lymphoma patients not achieving a complete metabolic response (CMR) on FDG-PET-CT scan after first or second line salvage therapy.
- Detailed Description
This is a single-arm, phase II, multi-centre study of the safety and efficacy of the programmed cell death protein 1 (PD-1) inhibitor, nivolumab, as second-line or third-line salvage therapy, and in particular as a bridge to stem cell transplant (SCT) in relapsed/ refractory classical Hodgkin lymphoma patients not achieving a complete metabolic response (CMR) on fluorodeoxyglucose positron emission tomography (FDG-PET) scan post first or second line salvage therapy.
Approximately 120 patients with relapsed/refractory classical Hodgkin lymphoma will be registered while undergoing first or second line salvage therapy (first line is preferred).
Patients will have a centrally reviewed PET CT scan after first or second line salvage therapy. Those with complete metabolic response (CMR) on PET CT scan (Deauville score 1-3) will not be eligible for trial treatment. They will be followed up for trial data collection purposes, and further management will be at their treating clinician's discretion.
Patients achieving less than CMR on central review of FDG-PET (Deauville score 4-5) will be eligible to receive up to 8 x 2-weekly nivolumab infusions. 30 patients will be treated on the trial.
After 4 courses of nivolumab, patients will have an additional centrally reviewed PET-CT scan (PET4). Patients achieving CMR will stop trial treatment, and enter follow up. Further treatment will be at their clinician's discretion but is likely to be stem cell transplant (SCT). Patients with partial metabolic response (PMR) or stable disease (SD) on PET4 will receive a further 4 cycles of nivolumab, again followed by a centrally reviewed PET-CT scan (PET8) to assess final response.
Further management after PET8 will be at the discretion of the treating clinician, although it is anticipated that those with CMR or PMR will proceed to SCT. If PET8 shows less than CMR (i.e. PMR or SD), patients who consent will have a further biopsy to exclude false positive PET signal; this will be centrally reviewed.
Patients with progressive metabolic disease (PMD) on nivolumab at any point will stop trial treatment. If a repeat biopsy is obtained to confirm progressive disease histologically, the biopsy material will be centrally reviewed.
Patients will be followed up for a minimum of 3 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 78
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nivolumab Nivolumab Up to 8 x 2-weekly cycles of nivolumab 240mg IV. Interim PET-CT scan to be performed after 4 cycles, and centrally reviewed. Patients will stop treatment after 4 cycles if they have complete metabolic response or progressive metabolic disease. If they have partial metabolic response or stable disease, they will continue to 8 cycles.
- Primary Outcome Measures
Name Time Method Overall response rate (ORR) by PET-CT scan following 4-8 cycles of nivolumab 4 months Rate of patients achieving complete metabolic response (CMR) on PET-CT scan following 4 or 8 cycles of nivolumab
- Secondary Outcome Measures
Name Time Method Progression-free survival 1 year Progression-free survival at 1 year; also to be analysed stratified by partial metabolic response vs complete metabolic response.
Adverse events [Safety and toxicity of nivolumab] 3 years Adverse events and serious adverse events occurring in patients treated with nivolumab, in particular autoimmune toxicity
Overall survival 1 year Overall survival at 1 year; also to be analysed stratified by partial metabolic response (PMR) vs complete metabolic response (CMR).
Transplant-related mortality 3 years Proportion of patients treated with nivolumab that subsequently die of transplant-related causes
Proportion of patients progressing to stem cell transplant 1 year Proportion of patients progressing to autologous or allogeneic stem cell transplant
Transplant-related morbidity 3 years Proportion of patients treated with nivolumab that go on to suffer serious complications of allogeneic transplant (grade 3-4 graft-versus-host disease, hyperacute graft-versus-host disease and steroid-responsive febrile syndrome)
Trial Locations
- Locations (10)
Royal Cornwall Hospital
🇬🇧Truro, Cornwall, United Kingdom
St Bartholomew's Hospital
🇬🇧London, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
St George's Hospital
🇬🇧London, United Kingdom
The Royal Marsden Hospital
🇬🇧London, United Kingdom
The Christie Hospital
🇬🇧Manchester, United Kingdom
Norfolk & Norwich University Hospital
🇬🇧Norwich, Norfolk, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom