Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study

NCT ID: NCT03617666

Last Updated: 2023-12-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-27
• Study Completion Date: 2025-05-30

Brief Summary

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.

Detailed Description

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).

Conditions

Hodgkin Lymphoma

Keywords

avelumab

Study Design

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

Study Groups

Avelumab

Patients with newly diagnosed cHL will receive single agent avelumab in 2 cycles

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

Patients with newly diagnosed cHL will receive 4 doses of single agent avelumab 10 mg/kg intravenously given every 2 weeks.

Interventions

Avelumab

Patients with newly diagnosed cHL will receive 4 doses of single agent avelumab 10 mg/kg intravenously given every 2 weeks.

Intervention Type: DRUG

Other Intervention Names

Bavencio

Eligibility Criteria

Inclusion Criteria

• Previously untreated classical Hodgkin lymphoma
• High risk stage II (defined as stage IIB, presence of bulky disease, 3 or more sites of disease), stage III or IV as assessed by FDG-PET/CT
• ECOG performance status 0-1
• Adequate bone marrow function (Hb >80g/l, Platelets >75 x 10^9/l, neutrophils >1.0 x 10^9/l)
• Adequate liver function tests (ALT/AST <2.5 x ULN, total serum bilirubin level <1.5 x ULN)
• Creatinine clearance >50ml/min calculated by Cockroft-Gault formula
• Written informed consent
• Willing to comply with the contraceptive requirements of the trial
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria

• Nodular lymphocyte predominant Hodgkin lymphoma
• Compressive symptoms due to disease (which may or may not be bulky). If there is evidence of compression of vital structures radiologically but the patient is asymptomatic, the case must be discussed with the TMG.
• Requirement for urgent treatment due to life-threatening complications of the disease
• Women who are pregnant or breastfeeding
• History of colitis, inflammatory bowel disease or pneumonitis
• Patients with autoimmune disorders excluding patients with vitiligo, diabetes mellitus type 1, hypo- and hyperthyroidism, coeliac disease not requiring immunosuppressive therapy
• Immunosuppressive therapy within the last 2 months, apart from inhaled, intranasal, topical corticosteroids or systemic corticosteroids at low doses (≤10mg prednisolone per day or equivalent - see steroid exception below)
• Prior history of solid organ or allogeneic haematopoietic stem cell transplant
• Positive serology for hepatitis B or C (unless due to vaccination), or hepatitis C RNA negative if hepatitis C antibody positive
• Known HIV infection
• Administration of a live vaccine within 30 days prior to study entry
• History of allergy to monoclonal antibodies, anaphylaxis or uncontrolled allergy
• Chemo- or radiotherapy within 15 days prior to registration. Corticosteroids permitted for disease control but must be weaned down to ≤10mg prednisolone per day or equivalent at least 7 days prior to starting avelumab - steroids may only be started for disease control after the baseline PET-CT
• Persisting toxicity (of >grade 1) related to prior therapy, however, alopecia, sensory neuropathy Grade <2, or other grade <2 not constituting a safety risk based on investigator's judgement are acceptable
• Major surgery within 4 weeks prior to registration
• Active infection requiring systemic therapy
• 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 (some exceptions apply)
• Previously treated haematological malignancy
• Any uncontrolled medical condition which can impair delivery of planned immunochemotherapy
• Patient not deemed suitable for ABVD/AVD/escalated-BEACOPP/BEACOPP-14

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Graham Collins

Role: PRINCIPAL_INVESTIGATOR

Churchill Hospital

Locations

Austin Health

Heidelberg, Victoria, Australia

Heartlands Hospital

Birmingham, , United Kingdom

Beatson Hospital

Glasgow, , United Kingdom

Leicester Royal Infirmary

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

The Royal Marsden Hospital, Sutton

Sutton, , United Kingdom

Countries

Australia; United Kingdom

Other Identifiers

2018-002227-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UCL /17/0192

Identifier Type: -

Identifier Source: org_study_id