This is a phase II, non-randomised, multicentre study to assess the safety and efficacy of the PD-L1 inhibitor, avelumab, in a previously untreated fit population of high risk stage II, stage III and stage IV classical Hodgkin lymphoma.
This phase II study investigates the safety and efficacy of the PD-L1 inhibitor, avelumab, in a previously untreated fit population of high risk stage II, stage III and stage IV classical Hodgkin lymphoma. Patients with newly diagnosed high risk stage II, stage III or stage IV cHL staged by 18FDG-PET/CT will receive 4 doses of single agent avelumab every 2 weeks. After the 4th dose of avelumab patients will have a PET-CT scan. All patients will then receive 2 cycles of ABVD followed by a PET-CT scan and further treatment will be guided in a risk-adapted manner based on the results of the RATHL. That is, patients who achieve PET CMR (defined as Deauville score 1-3) will receive 4 cycles of AVD and will undergo a CT scan. Patients with Deauville score 4-5 will receive 4 cycles of BEACOPP-14 or 3 cycles of escalated BEACOPP (at Investigators discretion and as per standard local policy) and will then undergo a further PET scan. Patients who are Deauville score 1-3 at this point will receive 2 further cycles of BEACOPP-14 or 1 cycle of escalated BEACOPP (at Investigators discretion and as per standard local policy). Patients who are Deauville score 4-5 at this point will receive further treatment at Investigators discretion and as per standard local policy. Radiotherapy to sites of residual avidity, initial bulk or as part of salvage treatment, is recommended (but not mandated).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Patients with newly diagnosed cHL will receive 4 doses of single agent avelumab 10 mg/kg intravenously given every 2 weeks.
Austin Health
Heidelberg, Victoria, Australia
Heartlands Hospital
Birmingham, United Kingdom
Beatson Hospital
Glasgow, United Kingdom
Leicester Royal Infirmary
Overall response rate
Overall response rate (complete metabolic response (CMR) and partial metabolic response (PMR)) after 2 months (4 doses) of single agent avelumab treatment
Time frame: 2 months (after first dose of avelumab)
Progression free survival
Progression free survival will be calculated from the date of registration until the date of progression.
Time frame: 1 year and 3 years (from date of registration)
Overall survival
Overall survival time will be calculated from the date of registration until the date of death.
Time frame: 1 year and 3 years (from date of registration)
Rates of adverse events with avelumab
Safety and toxicity of avelumab, particularly autoimmune toxicity, as assessed by CTCAE v5.0
Time frame: 3 months (after first dose of avelumab)
Rates of adverse events with ABVD/BEACOPP
Safety and toxicity of subsequent ABVD/BEACOPP based chemotherapy, as assessed by CTCAE v5.0
Time frame: 7 months (after commencing ABVD/BEACOPP)
Complete metabolic response rate
Complete metabolic response rate following 2 cycles of ABVD
Time frame: 2 months (after commencing ABVD)
Partial metabolic response rate
Partial metabolic response rate following 2 cycles of ABVD
Time frame: 2 months (after commencing ABVD)
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Leicester, United Kingdom
St George's Hospital
London, United Kingdom
Christie Hospital
Manchester, United Kingdom
Norfolk and Norwich University Hospital
Norwich, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Derriford Hospital
Plymouth, United Kingdom
Royal Stoke University Hospital
Stoke, United Kingdom
...and 1 more locations
Treatment compliance
Proportion of patients completing chemotherapy without delays/dose modifications and proportion of patients who have chemotherapy dose delay/modification.
Time frame: 9 months (from the date of registration)