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Trial record 1 of 1 for:    NCT03617666
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Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study (AVENuE)

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ClinicalTrials.gov Identifier: NCT03617666
Recruitment Status : Recruiting
First Posted : August 6, 2018
Last Update Posted : November 4, 2020
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University College, London

Tracking Information
First Submitted Date  ICMJE July 20, 2018
First Posted Date  ICMJE August 6, 2018
Last Update Posted Date November 4, 2020
Actual Study Start Date  ICMJE September 27, 2019
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2018)
  • 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.
  • 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.
  • 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
  • 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
  • Complete metabolic response rate [ Time Frame: 2 months (after commencing ABVD) ]
    Complete metabolic response rate following 2 cycles of ABVD
  • Partial metabolic response rate [ Time Frame: 2 months (after commencing ABVD) ]
    Partial metabolic response rate following 2 cycles of ABVD
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 31, 2018)
  • 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)
  • 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
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study
Official Title  ICMJE AVENuE - Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hodgkin Lymphoma
Intervention  ICMJE Drug: Avelumab
Patients with newly diagnosed cHL will receive 4 doses of single agent avelumab intravenously given every 2 weeks.
Study Arms  ICMJE Experimental: Avelumab
Patients with newly diagnosed cHL will receive single agent avelumab in 2 cycles
Intervention: Drug: Avelumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 31, 2018)
47
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2024
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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)
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Emma Barsoum +44 (0)207 679 9860 ctc.avenue@ucl.ac.uk
Contact: Richard Jenner +44 (0)207 679 9860 ctc.avenue@ucl.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03617666
Other Study ID Numbers  ICMJE UCL /17/0192
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University College, London
Study Sponsor  ICMJE University College, London
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Graham Collins Churchill Hospital
PRS Account University College, London
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP