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

Primary Purpose

Hodgkin Lymphoma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Avelumab
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkin Lymphoma focused on measuring avelumab

Eligibility Criteria

16 Years - 60 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Austin Health
  • Heartlands Hospital
  • Beatson Hospital
  • Leicester Royal Infirmary
  • St George's Hospital
  • Christie Hospital
  • Norfolk and Norwich University Hospital
  • Churchill Hospital
  • Derriford Hospital
  • The Royal Marsden Hospital, Sutton

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Avelumab

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Progression free survival
Progression free survival will be calculated from the date of registration until the date of progression.
Overall survival
Overall survival time will be calculated from the date of registration until the date of death.
Rates of adverse events with avelumab
Safety and toxicity of avelumab, particularly autoimmune toxicity, as assessed by CTCAE v5.0
Rates of adverse events with ABVD/BEACOPP
Safety and toxicity of subsequent ABVD/BEACOPP based chemotherapy, as assessed by CTCAE v5.0
Complete metabolic response rate
Complete metabolic response rate following 2 cycles of ABVD
Partial metabolic response rate
Partial metabolic response rate following 2 cycles of ABVD
Treatment compliance
Proportion of patients completing chemotherapy without delays/dose modifications and proportion of patients who have chemotherapy dose delay/modification.

Full Information

First Posted
July 20, 2018
Last Updated
October 31, 2022
Sponsor
University College, London
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT03617666
Brief Title
Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study
Acronym
AVENuE
Official Title
AVENuE - Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 27, 2019 (Actual)
Primary Completion Date
July 4, 2022 (Actual)
Study Completion Date
November 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
Pfizer

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma
Keywords
avelumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Avelumab
Arm Type
Experimental
Arm Description
Patients with newly diagnosed cHL will receive single agent avelumab in 2 cycles
Intervention Type
Drug
Intervention Name(s)
Avelumab
Other Intervention Name(s)
Bavencio
Intervention Description
Patients with newly diagnosed cHL will receive 4 doses of single agent avelumab 10 mg/kg intravenously given every 2 weeks.
Primary Outcome Measure Information:
Title
Overall response rate
Description
Overall response rate (complete metabolic response (CMR) and partial metabolic response (PMR)) after 2 months (4 doses) of single agent avelumab treatment
Time Frame
2 months (after first dose of avelumab)
Secondary Outcome Measure Information:
Title
Progression free survival
Description
Progression free survival will be calculated from the date of registration until the date of progression.
Time Frame
1 year (from date of registration)
Title
Overall survival
Description
Overall survival time will be calculated from the date of registration until the date of death.
Time Frame
1 year (from date of registration)
Title
Rates of adverse events with avelumab
Description
Safety and toxicity of avelumab, particularly autoimmune toxicity, as assessed by CTCAE v5.0
Time Frame
3 months (after first dose of avelumab)
Title
Rates of adverse events with ABVD/BEACOPP
Description
Safety and toxicity of subsequent ABVD/BEACOPP based chemotherapy, as assessed by CTCAE v5.0
Time Frame
7 months (after commencing ABVD/BEACOPP)
Title
Complete metabolic response rate
Description
Complete metabolic response rate following 2 cycles of ABVD
Time Frame
2 months (after commencing ABVD)
Title
Partial metabolic response rate
Description
Partial metabolic response rate following 2 cycles of ABVD
Time Frame
2 months (after commencing ABVD)
Title
Treatment compliance
Description
Proportion of patients completing chemotherapy without delays/dose modifications and proportion of patients who have chemotherapy dose delay/modification.
Time Frame
9 months (from the date of registration)
Other Pre-specified Outcome Measures:
Title
Correlate PET positive disease
Description
Correlate PET positive disease with histological evidence of disease on biopsy to establish biopsy negative PMR rate (subject to patient consent)
Time Frame
End of trial (3 years)
Title
Correlate disease response
Description
Correlate disease response, as assessed by FDG-PET and histology, with serological markers, including serum TARC
Time Frame
End of trial (3 years)
Title
Correlation between response to avelumab and biological parameter
Description
Evaluate the correlation between response to avelumab and biological parameters e.g. PD-1 expression on Reed Sternberg cells
Time Frame
End of trial (3 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Graham Collins
Organizational Affiliation
Churchill Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
Country
Australia
Facility Name
Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Beatson Hospital
City
Glasgow
Country
United Kingdom
Facility Name
Leicester Royal Infirmary
City
Leicester
Country
United Kingdom
Facility Name
St George's Hospital
City
London
Country
United Kingdom
Facility Name
Christie Hospital
City
Manchester
Country
United Kingdom
Facility Name
Norfolk and Norwich University Hospital
City
Norwich
Country
United Kingdom
Facility Name
Churchill Hospital
City
Oxford
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
Country
United Kingdom
Facility Name
The Royal Marsden Hospital, Sutton
City
Sutton
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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

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