Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03617666
Other study ID # UCL /17/0192
Secondary ID 2018-002227-42
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date September 27, 2019
Est. completion date May 30, 2025

Study information

Verified date December 2023
Source University College, London
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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).


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 49
Est. completion date May 30, 2025
Est. primary completion date July 4, 2022
Accepts healthy volunteers No
Gender All
Age group 16 Years to 60 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Avelumab
Patients with newly diagnosed cHL will receive 4 doses of single agent avelumab 10 mg/kg intravenously given every 2 weeks.

Locations

Country Name City State
Australia Austin Health Heidelberg Victoria
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 Royal Stoke University Hospital Stoke
United Kingdom The Royal Marsden Hospital, Sutton Sutton

Sponsors (2)

Lead Sponsor Collaborator
University College, London Pfizer

Countries where clinical trial is conducted

Australia,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Correlate PET positive disease Correlate PET positive disease with histological evidence of disease on biopsy to establish biopsy negative PMR rate (subject to patient consent) End of trial (3 years)
Other Correlate disease response Correlate disease response, as assessed by FDG-PET and histology, with serological markers, including serum TARC End of trial (3 years)
Other Correlation between response to avelumab and biological parameter Evaluate the correlation between response to avelumab and biological parameters e.g. PD-1 expression on Reed Sternberg cells End of trial (3 years)
Primary 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 2 months (after first dose of avelumab)
Secondary Progression free survival Progression free survival will be calculated from the date of registration until the date of progression. 1 year and 3 years (from date of registration)
Secondary Overall survival Overall survival time will be calculated from the date of registration until the date of death. 1 year and 3 years (from date of registration)
Secondary Rates of adverse events with avelumab Safety and toxicity of avelumab, particularly autoimmune toxicity, as assessed by CTCAE v5.0 3 months (after first dose of avelumab)
Secondary Rates of adverse events with ABVD/BEACOPP Safety and toxicity of subsequent ABVD/BEACOPP based chemotherapy, as assessed by CTCAE v5.0 7 months (after commencing ABVD/BEACOPP)
Secondary Complete metabolic response rate Complete metabolic response rate following 2 cycles of ABVD 2 months (after commencing ABVD)
Secondary Partial metabolic response rate Partial metabolic response rate following 2 cycles of ABVD 2 months (after commencing ABVD)
Secondary Treatment compliance Proportion of patients completing chemotherapy without delays/dose modifications and proportion of patients who have chemotherapy dose delay/modification. 9 months (from the date of registration)
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Recruiting NCT05019976 - Radiation Dose Study for Relapsed/Refractory Hodgkin/Non-Hodgkin Lymphoma N/A
Completed NCT04666025 - SARS-CoV-2 Donor-Recipient Immunity Transfer
Recruiting NCT02507479 - Thiotepa-based Conditioning for Allogeneic Stem-cell Transplantation (SCT) in Lymphoid Malignancies Phase 2
Active, not recruiting NCT02191930 - Brentuximab Vedotin or B-CAP in the Treatment of Older Patients With Newly Diagnosed Classical Hodgkin Lymphoma Phase 2
Completed NCT01943682 - Safety Study of CPX-351 in Children With Relapsed Leukemia or Lymphoma Phase 1
Completed NCT01393106 - Safety and Efficacy of Idelalisib in Relapsed or Refractory Hodgkin Lymphoma Phase 2
Terminated NCT00992030 - R-ABVD vs ABVD-RT in Early Stage Hodgkin's Lymphoma Phase 3
Terminated NCT00722865 - Avastin (Bevacizumab) Plus Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) for Advanced Stage Hodgkin Lymphoma Phase 2
Unknown status NCT00598624 - Clinical Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) Phase 2
Completed NCT03242902 - To Decrease Fatigue With Light Therapy Phase 3
Active, not recruiting NCT05205512 - Telehealth Exercise Intervention to Improve Cardiovascular Health in Lymphoma Survivors, TECHS Trial N/A
Recruiting NCT03681561 - Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma Phase 1/Phase 2
Recruiting NCT03250962 - SHR-1210 Alone or in Combination With Decitabine in Relapsed or Refractory Hodgkin Lymphoma Phase 2
Recruiting NCT04510610 - Camrelizumab Plus Decitabine in Anti-PD-1 Treatment-naive Patients With Relapsed/Refractory Classical Hodgkin Lymphoma Phase 2/Phase 3
Completed NCT06295211 - Brentuximab Vedotin Combined With Bendamustine Supercharge, a Low-toxicity and Efficient Salvage Regimen for Primary Refractory or First-relapsed Classic Hodgkin Lymphoma: Long-term Results of a Retrospective Monocenter Study.
Active, not recruiting NCT02256137 - A Longitudinal Assessment of Frailty in Young Adult Survivors of Childhood Cancer
Completed NCT02432235 - Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma Phase 1
Completed NCT02572167 - A Study of Brentuximab Vedotin Combined With Nivolumab for Relapsed or Refractory Hodgkin Lymphoma Phase 1/Phase 2