ANIMATE: Phase II Study of Nivolumab Monotherapy for Relapsed/Refractory Hodgkin Lymphoma (ANIMATE)
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|ClinicalTrials.gov Identifier: NCT03337919|
Recruitment Status : Recruiting
First Posted : November 9, 2017
Last Update Posted : December 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Hodgkin Lymphoma||Drug: Nivolumab||Phase 2|
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 2 cycles of 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 2 cycles of the salvage therapy they are receiving (or 4 cycles if they are undergoing treatment with brentuximab vedotin). 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a single-arm, phase II, multi-centre study. It will use an Ahern single stage design with independent trials steering committee review to monitor for safety and efficacy.|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Nivolumab Monotherapy in Patients With Relapsed/Refractory Hodgkin Lymphoma Fit for Autologous Stem Cell Transplant Who Fail to Reach Complete Metabolic Remission After First or Second Line Salvage Therapy|
|Actual Study Start Date :||December 3, 2018|
|Estimated Primary Completion Date :||May 2022|
|Estimated Study Completion Date :||May 2025|
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.
Up to 8 cycles of nivolumab
Other Name: Opdivo®
- Overall response rate (ORR) by PET-CT scan following 4-8 cycles of nivolumab [ Time Frame: 4 months ]Rate of patients achieving complete metabolic response (CMR) on PET-CT scan following 4 or 8 cycles of nivolumab
- Progression-free survival [ Time Frame: 1 year ]Progression-free survival at 1 year; also to be analysed stratified by partial metabolic response vs complete metabolic response.
- Overall survival [ Time Frame: 1 year ]Overall survival at 1 year; also to be analysed stratified by partial metabolic response (PMR) vs complete metabolic response (CMR).
- Proportion of patients progressing to stem cell transplant [ Time Frame: 1 year ]Proportion of patients progressing to autologous or allogeneic stem cell transplant
- Adverse events [Safety and toxicity of nivolumab] [ Time Frame: 3 years ]Adverse events and serious adverse events occurring in patients treated with nivolumab, in particular autoimmune toxicity
- Transplant-related mortality [ Time Frame: 3 years ]Proportion of patients treated with nivolumab that subsequently die of transplant-related causes
- Transplant-related morbidity [ Time Frame: 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)
- Biopsy-negative PMR rate [ Time Frame: 4 months ]Correlation of PET positive disease with histological evidence of disease on post-treatment repeat biopsy to establish biopsy negative PMR rate (subject to patient consent)
- Serological biomarkers of response to nivolumab [ Time Frame: 5 months ]Correlation of disease response with serological markers such as serum Thymus and activation-regulated chemokine (TARC) levels
- Immunological biomarkers of response to treatment [ Time Frame: 4 months ]Evaluate the correlation between response to nivolumab and biological parameters e.g. PD-L1 expression on Reed Sternberg cells
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03337919
|Contact: Oliver Schofield||+44 (0)20 7679 firstname.lastname@example.org|
|Leicester Royal Infirmary||Recruiting|
|Leicester, United Kingdom, LE1 5WW|
|Contact: Thomas Rogers 0116 258 5951 email@example.com|
|Principal Investigator: Fiona Miall|
|Oxford, United Kingdom, OX3 7LE|
|Contact: Reihaneh Emami 01865 235309 Trialadministrator07@oncology.ox.ac.uk|
|Principal Investigator: Graham Collins|
|Principal Investigator:||Graham Collins||Oxford University Hospitals NHS Trust|