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

University College London (UCL)

Status and phase

Active, not recruiting

Phase 2

Conditions

Hodgkin Lymphoma

Treatments

Drug: Avelumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03617666

UCL /17/0192

2018-002227-42 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment

49 patients

Sex

All

Ages

16 to 60 years old

Volunteers

No Healthy Volunteers

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