Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03617666
Recruitment Status : Active, not recruiting
First Posted : August 6, 2018
Last Update Posted : May 11, 2022
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University College, London

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.

Condition or disease Intervention/treatment Phase
Hodgkin Lymphoma Drug: Avelumab Phase 2

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: AVENuE - Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study
Actual Study Start Date : September 27, 2019
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : November 1, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

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 Name: Bavencio




Primary Outcome Measures :
  1. Overall response rate [ Time Frame: 2 months (after first dose of avelumab) ]
    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 :
  1. Progression free survival [ Time Frame: 1 year (from date of registration) ]
    Progression free survival will be calculated from the date of registration until the date of progression.

  2. Overall survival [ Time Frame: 1 year (from date of registration) ]
    Overall survival time will be calculated from the date of registration until the date of death.

  3. Rates of adverse events with avelumab [ Time Frame: 3 months (after first dose of avelumab) ]
    Safety and toxicity of avelumab, particularly autoimmune toxicity, as assessed by CTCAE v5.0

  4. Rates of adverse events with ABVD/BEACOPP [ Time Frame: 7 months (after commencing ABVD/BEACOPP) ]
    Safety and toxicity of subsequent ABVD/BEACOPP based chemotherapy, as assessed by CTCAE v5.0

  5. Complete metabolic response rate [ Time Frame: 2 months (after commencing ABVD) ]
    Complete metabolic response rate following 2 cycles of ABVD

  6. Partial metabolic response rate [ Time Frame: 2 months (after commencing ABVD) ]
    Partial metabolic response rate following 2 cycles of ABVD

  7. Treatment compliance [ Time Frame: 9 months (from the date of registration) ]
    Proportion of patients completing chemotherapy without delays/dose modifications and proportion of patients who have chemotherapy dose delay/modification.


Other Outcome Measures:
  1. Correlate PET positive disease [ Time Frame: End of trial (3 years) ]
    Correlate PET positive disease with histological evidence of disease on biopsy to establish biopsy negative PMR rate (subject to patient consent)

  2. Correlate disease response [ Time Frame: End of trial (3 years) ]
    Correlate disease response, as assessed by FDG-PET and histology, with serological markers, including serum TARC

  3. Correlation between response to avelumab and biological parameter [ Time Frame: End of trial (3 years) ]
    Evaluate the correlation between response to avelumab and biological parameters e.g. PD-1 expression on Reed Sternberg cells



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03617666


Locations
Layout table for location information
Australia, Victoria
Austin Health
Heidelberg, Victoria, Australia
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
The Royal Marsden Hospital, Sutton
Sutton, United Kingdom
Sponsors and Collaborators
University College, London
Pfizer
Investigators
Layout table for investigator information
Principal Investigator: Graham Collins Churchill Hospital
Layout table for additonal information
Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT03617666    
Other Study ID Numbers: UCL /17/0192
2018-002227-42 ( EudraCT Number )
First Posted: August 6, 2018    Key Record Dates
Last Update Posted: May 11, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Keywords provided by University College, London:
avelumab
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Avelumab
Antineoplastic Agents, Immunological
Antineoplastic Agents