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

Hodgkin Lymphoma Clinical Trial

— AVENuE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03617666
• Other study ID #: UCL /17/0192
• Secondary ID: 2018-002227-42
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 27, 2019
• Est. completion date: May 30, 2025

Study information

• Verified date: December 2023
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 49
• Est. completion date: May 30, 2025
• Est. primary completion date: July 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

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

Locations

Country	Name	City	State
Australia	Austin Health	Heidelberg	Victoria
United Kingdom	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

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Pfizer

Countries where clinical trial is conducted

Australia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlate PET positive disease	Correlate PET positive disease with histological evidence of disease on biopsy to establish biopsy negative PMR rate (subject to patient consent)	End of trial (3 years)
Other	Correlate disease response	Correlate disease response, as assessed by FDG-PET and histology, with serological markers, including serum TARC	End of trial (3 years)
Other	Correlation between response to avelumab and biological parameter	Evaluate the correlation between response to avelumab and biological parameters e.g. PD-1 expression on Reed Sternberg cells	End of trial (3 years)
Primary	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	2 months (after first dose of avelumab)
Secondary	Progression free survival	Progression free survival will be calculated from the date of registration until the date of progression.	1 year and 3 years (from date of registration)
Secondary	Overall survival	Overall survival time will be calculated from the date of registration until the date of death.	1 year and 3 years (from date of registration)
Secondary	Rates of adverse events with avelumab	Safety and toxicity of avelumab, particularly autoimmune toxicity, as assessed by CTCAE v5.0	3 months (after first dose of avelumab)
Secondary	Rates of adverse events with ABVD/BEACOPP	Safety and toxicity of subsequent ABVD/BEACOPP based chemotherapy, as assessed by CTCAE v5.0	7 months (after commencing ABVD/BEACOPP)
Secondary	Complete metabolic response rate	Complete metabolic response rate following 2 cycles of ABVD	2 months (after commencing ABVD)
Secondary	Partial metabolic response rate	Partial metabolic response rate following 2 cycles of ABVD	2 months (after commencing ABVD)
Secondary	Treatment compliance	Proportion of patients completing chemotherapy without delays/dose modifications and proportion of patients who have chemotherapy dose delay/modification.	9 months (from the date of registration)