ANIMATE: Phase II Study of Nivolumab Monotherapy for Relapsed/Refractory Hodgkin Lymphoma

NCT ID: NCT03337919

Last Updated: 2024-05-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-03
• Study Completion Date: 2026-02-28

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.

Conditions

Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Up to 8 cycles of nivolumab

Interventions

Nivolumab

Up to 8 cycles of nivolumab

Intervention Type: DRUG

Other Intervention Names

Opdivo®

Eligibility Criteria

Inclusion Criteria

1. Age 16 or over

2. Primary refractory classical Hodgkin lymphoma or classical Hodgkin lymphoma in first relapse

3. About to receive or receiving first or second line salvage therapy (up to a maximum of 14 days after last treatment)

4. Fit for autologous stem cell transplantation

5. Written informed consent

6. Willing to comply with the contraceptive requirements of the trial

1. Has received 2 cycles of first or second line salvage chemotherapy

2. PET positive (Deauville score 4 or 5) after first or second line salvage chemotherapy

3. Fit for further salvage chemotherapy

4. ECOG performance status 0-1

5. Creatinine clearance >30ml/min calculated by Cockcroft-Gault formula

6. Bilirubin <1.5 x ULN, ALT/AST <2.5 x ULN

7. Adequate bone marrow function (Hb >80g/l, Platelets >50 x 10^9/l, neutrophils >1.0 x 10^9/l)

Exclusion Criteria

1. Nodular lymphocyte predominant Hodgkin lymphoma

2. Women who are pregnant or breastfeeding

3. History of colitis, inflammatory bowel disease or pneumonitis

4. Patients with autoimmune disorders, except patients with vitiligo, diabetes mellitus type 1, hypo- and hyperthyroidism not requiring immunosuppressive therapy

5. Known history of hepatitis B or C infection

6. Known HIV infection

7. History of allergy (including severe/life threatening skin reaction) to monoclonal antibodies, anaphylaxis or uncontrolled allergy

8. Major surgery within 4 weeks prior to registration

9. Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within the past 6 months

10. Non-haematological malignancy within the past 3 years (with some exceptions - listed in protocol)

1. Deauville score 1-3 after first or second line salvage chemotherapy

2. Positive serology for hepatitis B or C (some exclusions apply - see protocol)

3. Active infection requiring systemic therapy

4. Ongoing requirement for immunosuppressive therapy, apart from inhaled, intranasal, topical corticosteroids or systemic corticosteroids at low doses (≤10mg prednisolone per day, or the equivalent)

5. 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.

6. Treatment with any investigational agent within 28 days prior to planned start of nivolumab

7. Ongoing grade 2-4 non-haematological toxicities related to prior Hodgkin lymphoma treatments, with the exception of alopecia and grade 2 fatigue

8. Pregnant or breastfeeding women

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Graham Collins

Role: PRINCIPAL_INVESTIGATOR

Oxford University Hospitals NHS Trust

Locations

Royal Cornwall Hospital

Truro, Cornwall, United Kingdom

Norfolk & Norwich University Hospital

Norwich, Norfolk, United Kingdom

The Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Leicester Royal Infirmary

Leicester, , United Kingdom

St Bartholomew's Hospital

London, , United Kingdom

Guy's Hospital

London, , United Kingdom

St George's Hospital

London, , United Kingdom

The Royal Marsden Hospital

London, , United Kingdom

The Christie Hospital

Manchester, , United Kingdom

Churchill Hospital

Oxford, , United Kingdom

Countries

United Kingdom

Related Links

http://www.ctc.ucl.ac.uk/

CR UK \& UCL Cancer Trials Centre

Other Identifiers

CA-209-445

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2017-002544-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UCL/15/0515

Identifier Type: -

Identifier Source: org_study_id