Hodgkin LymphomaPhase 2ANIMATENCT03337919
ANIMATE: Phase II Study of Nivolumab Monotherapy for Relapsed/Refractory Hodgkin Lymphoma
A Phase 2 study testing Nivolumab in people with Hodgkin Lymphoma, run by University College, London at 10 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Hodgkin Lymphoma
- What is being tested?
- Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 10 sitesUnited Kingdom
- Study dates
- 3 Dec 2018to 28 Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16 or over
- Primary refractory classical Hodgkin lymphoma or classical Hodgkin lymphoma in first relapse
- About to receive or receiving first or second line salvage therapy (up to a maximum of 14 days after last treatment)
- Fit for autologous stem cell transplantation
- Written informed consent
- Willing to comply with the contraceptive requirements of the trial
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- Has received 2 cycles of first or second line salvage chemotherapy
- PET positive (Deauville score 4 or 5) after first or second line salvage chemotherapy
- Fit for further salvage chemotherapy
- ECOG performance status 0-1
- Creatinine clearance >30ml/min calculated by Cockcroft-Gault formula
- Bilirubin <1.5 x ULN, ALT/AST <2.5 x ULN
- Adequate bone marrow function (Hb >80g/l, Platelets >50 x 10^9/l, neutrophils >1.0 x 10^9/l)
Who cannot join
- Nodular lymphocyte predominant Hodgkin lymphoma
- Women who are pregnant or breastfeeding
- History of colitis, inflammatory bowel disease or pneumonitis
- Patients with autoimmune disorders, except patients with vitiligo, diabetes mellitus type 1, hypo- and hyperthyroidism not requiring immunosuppressive therapy
- Known history of hepatitis B or C infection
- Known HIV infection
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- History of allergy (including severe/life threatening skin reaction) to monoclonal antibodies, anaphylaxis or uncontrolled allergy
- Major surgery within 4 weeks prior to registration
- Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within the past 6 months
- Non-haematological malignancy within the past 3 years (with some exceptions - listed in protocol)
- Deauville score 1-3 after first or second line salvage chemotherapy
- Positive serology for hepatitis B or C (some exclusions apply - see protocol)
- Active infection requiring systemic therapy
- Ongoing requirement for immunosuppressive therapy, apart from inhaled, intranasal, topical corticosteroids or systemic corticosteroids at low doses (≤10mg prednisolone per day, or the equivalent)
- Corticosteroids at a dose of more than 10mg per day prednisolone or equivalent within 7 days prior to response PET-CT. NOTE: corticosteroids can be used AFTER a positive PET-CT scan for symptomatic disease but must be weaned to a dose of prednisolone ≤10mg/day or less (or equivalent) at least 7 days prior to starting nivolumab.
- Treatment with any investigational agent within 28 days prior to planned start of nivolumab
- Ongoing grade 2-4 non-haematological toxicities related to prior Hodgkin lymphoma treatments, with the exception of alopecia and grade 2 fatigue
- Pregnant or breastfeeding women
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United Kingdom10 sites
The Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Leicester Royal Infirmary
Leicester, LE1 5WW
St Bartholomew's Hospital
London, EC1A 7BE
Guy's Hospital
London, SE1 9RT
St George's Hospital
London, SW17 0QT
The Royal Marsden Hospital
London, SW3 6JJ
The Christie Hospital
Manchester, M20 4BX
Norfolk & Norwich University Hospital
Norwich, Norfolk, NR4 7UY
Churchill Hospital
Oxford, OX3 7LE
Royal Cornwall Hospital
Truro, Cornwall, TR1 3LQ
About this study
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
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.
Read the 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.
- Conditions
- Hodgkin Lymphoma
- Being tested
- Nivolumab
- Keywords
- Nivolumab
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo®
Up to 8 cycles of nivolumab
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab | Experimental | 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. Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR) by PET-CT scan following 4-8 cycles of nivolumab
Rate of patients achieving complete metabolic response (CMR) on PET-CT scan following 4 or 8 cycles of nivolumab
Measured: 4 months
Secondary outcomes (6)
Progression-free survival
Progression-free survival at 1 year; also to be analysed stratified by partial metabolic response vs complete metabolic response.
Measured: 1 year
Overall survival
Overall survival at 1 year; also to be analysed stratified by partial metabolic response (PMR) vs complete metabolic response (CMR).
Measured: 1 year
Proportion of patients progressing to stem cell transplant
Proportion of patients progressing to autologous or allogeneic stem cell transplant
Measured: 1 year
Adverse events [Safety and toxicity of nivolumab]
Adverse events and serious adverse events occurring in patients treated with nivolumab, in particular autoimmune toxicity
Measured: 3 years
Transplant-related mortality
Proportion of patients treated with nivolumab that subsequently die of transplant-related causes
Measured: 3 years
Transplant-related morbidity
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)
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2017
- Study start3 Dec 2018
- Primary completion1 Mar 2023
- Study completion28 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Graham Collins, Principal investigator, Oxford University Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03337919
- Sponsor's protocol ID
- UCL/15/0515
- Other IDs
- CA-209-445, 2017-002544-32, 2017
- Acronym
- ANIMATE
- Status last verified
- May 2024
- First submitted
- 26 Oct 2017
- Last updated
- 10 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03337919
- Acronym / sponsor ID
- ANIMATE / UCL/15/0515
- Conditions
- Hodgkin Lymphoma
- Keywords
- Nivolumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 78 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 3 Dec 2018 (actual)
- Primary completion
- 1 Mar 2023 (actual)
- Study completion
- 28 Feb 2026 (estimated)
- First posted
- 9 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Nivolumab | Experimental | Drug: NivolumabUp 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Age 16 or over
- Primary refractory classical Hodgkin lymphoma or classical Hodgkin lymphoma in first relapse
- About to receive or receiving first or second line salvage therapy (up to a maximum of 14 days after last treatment)
- Fit for autologous stem cell transplantation
- Written informed consent
Key exclusion criteria (18 listed)
- Nodular lymphocyte predominant Hodgkin lymphoma
- Women who are pregnant or breastfeeding
- History of colitis, inflammatory bowel disease or pneumonitis
- Patients with autoimmune disorders, except patients with vitiligo, diabetes mellitus type 1, hypo- and hyperthyroidism not requiring immunosuppressive therapy
- Known history of hepatitis B or C infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: Opdivo®Up to 8 cycles of nivolumab | Drug | Nivolumab |
Primary outcome
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
6 secondary outcomes
Progression-free survival
Time frame: 1 year
Overall survival
Time frame: 1 year
Proportion of patients progressing to stem cell transplant
Time frame: 1 year
Adverse events [Safety and toxicity of nivolumab]
Time frame: 3 years
Transplant-related mortality
Time frame: 3 years
Transplant-related morbidity
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
- CR UK \& UCL Cancer Trials CentreLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Graham Collins principal investigator
Oxford University Hospitals NHS Trust
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab in people with Hodgkin Lymphoma, run by University College, London at 10 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) by PET-CT scan following 4-8 cycles of nivolumab (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2024.