Clinical trial NCT03617666: Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study
Official title: AVENuE - Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Keywords: avelumab
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2018-08-06
Enrollment: 49
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Overall response rate
timeFrame: 2 months (after first dose of avelumab)
Secondary outcomes:
measure: Progression free survival
timeFrame: 1 year and 3 years (from date of registration)
measure: Overall survival
timeFrame: 1 year and 3 years (from date of registration)
measure: Rates of adverse events with avelumab
timeFrame: 3 months (after first dose of avelumab)
measure: Rates of adverse events with ABVD/BEACOPP
timeFrame: 7 months (after commencing ABVD/BEACOPP)
measure: Complete metabolic response rate
timeFrame: 2 months (after commencing ABVD)
measure: Partial metabolic response rate
timeFrame: 2 months (after commencing ABVD)
measure: Treatment compliance
timeFrame: 9 months (from the date of registration)
Other outcomes:
measure: Correlate PET positive disease
timeFrame: End of trial (3 years)
measure: Correlate disease response
timeFrame: End of trial (3 years)
measure: Correlation between response to avelumab and biological parameter
timeFrame: End of trial (3 years)
Locations:
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital
city: Glasgow
country: United Kingdom
facility: Beatson Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: St George's Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Stoke
country: United Kingdom
facility: Royal Stoke University Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital, Sutton
Study officials:
affiliation: Churchill Hospital
name: Graham Collins
role: PRINCIPAL_INVESTIGATOR
References: