Clinical Trials /

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

NCT03617666

Description:

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.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: UCL /17/0192
  • NCT ID: NCT03617666

Conditions

  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
AvelumabAvelumab

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
AvelumabExperimentalPatients with newly diagnosed cHL will receive single agent avelumab in 2 cycles
  • Avelumab

Eligibility Criteria

        Inclusion Criteria:

          -  Previously untreated classical Hodgkin lymphoma

          -  High risk stage II (defined as stage IIB, presence of bulky disease or 3 or more sites
             of disease), stage III or IV as assessed by FDG-PET/CT

          -  Sufficient remaining biopsy material for at least 10 unstained slides

          -  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)

          -  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)

          -  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
      
Maximum Eligible Age:60 Years
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:2 months (after first dose of avelumab)
Safety Issue:
Description: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

Measure:Progression free survival
Time Frame:1 year (from date of registration)
Safety Issue:
Description:Progression free survival will be calculated from the date of registration until the date of progression.
Measure:Overall survival
Time Frame:1 year (from date of registration)
Safety Issue:
Description:Overall survival time will be calculated from the date of registration until the date of death.
Measure:Rates of adverse events with avelumab
Time Frame:3 months (after first dose of avelumab)
Safety Issue:
Description:Safety and toxicity of avelumab, particularly autoimmune toxicity, as assessed by CTCAE v5.0
Measure:Rates of adverse events with ABVD/BEACOPP
Time Frame:7 months (after commencing ABVD/BEACOPP)
Safety Issue:
Description:Safety and toxicity of subsequent ABVD/BEACOPP based chemotherapy, as assessed by CTCAE v5.0
Measure:Complete metabolic response rate
Time Frame:2 months (after commencing ABVD)
Safety Issue:
Description:Complete metabolic response rate following 2 cycles of ABVD
Measure:Partial metabolic response rate
Time Frame:2 months (after commencing ABVD)
Safety Issue:
Description:Partial metabolic response rate following 2 cycles of ABVD
Measure:Treatment compliance
Time Frame:9 months (from the date of registration)
Safety Issue:
Description:Proportion of patients completing chemotherapy without delays/dose modifications and proportion of patients who have chemotherapy dose delay/modification.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University College, London

Trial Keywords

  • avelumab

Last Updated

February 25, 2020