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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Avelumab | | Avelumab |
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
| Name | Type | Description | Interventions |
|---|
| Avelumab | Experimental | Patients with newly diagnosed cHL will receive single agent avelumab in 2 cycles | |
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
- 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
| 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
Last Updated
November 4, 2020
