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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Drug: Avelumab

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).

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia
      • Austin Health
• United Kingdom
  • Birmingham, United Kingdom
    • Heartlands Hospital
  • Glasgow, United Kingdom
    • Beatson Hospital
  • Leicester, United Kingdom
    • Leicester Royal Infirmary
  • London, United Kingdom
    • St George's Hospital
  • Manchester, United Kingdom
    • Christie Hospital
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospital
  • Oxford, United Kingdom
    • Churchill Hospital
  • Plymouth, United Kingdom
    • Derriford Hospital
  • Stoke, United Kingdom
    • Royal Stoke University Hospital
  • Sutton, United Kingdom
    • The Royal Marsden Hospital, Sutton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Avelumab; Patients with newly diagnosed cHL will receive single agent avelumab in 2 cycles	Drug: Avelumab; Patients with newly diagnosed cHL will receive 4 doses of single agent avelumab 10 mg/kg intravenously given every 2 weeks.; Other Names: Bavencio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
Complete metabolic response rate	Complete metabolic response rate following 2 cycles of ABVD	2 months (after commencing ABVD)
Partial metabolic response rate	Partial metabolic response rate following 2 cycles of ABVD	2 months (after commencing ABVD)
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)
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)
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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Correlate disease response	Correlate disease response, as assessed by FDG-PET and histology, with serological markers, including serum TARC	End of trial (3 years)
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)

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Pfizer
• Investigators: Principal Investigator: Graham Collins, Churchill Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2019
• Primary Completion (Actual): July 4, 2022
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: July 20, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: avelumab
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: UCL /17/0192; 2018-002227-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No