Topic: National Cancer Research Network
Conditions
Interventions
Brentuximab vedotin: Antibody-drug conjugate
30 patients will be recruited from hospitals across the UK and will receive a maximum of 16 doses over 48 weeks.
Sponsors
University of Birmingham (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 18/05/2018: 1. Histologically confirmed CD30 positive classical Hodgkin lymphoma 2. No previous treatment for classical Hodgkin lymphoma 3. Aged more than or equal to 16 years 4. Stages II (with B symptoms, extranodal disease, bulky disease, more than or equal to sites of nodal involvement, fewer than 3 sites of nodal involvement but unsuitable for radiotherapy because of anatomical distribution or ESR more than or equal to 50 mm/h), III and IV classical Hodgkin lymphoma 5. Any of the following: At any age and with ECOG score of 0, 1, 2 or 3, for whom standard chemotherapy considered inappropriate because: 5.1. Impaired cardiac function defined either by an ejection fraction of 1.5 cm in long axis diameter (for nodal lesions) or >1.0cm in long axis diameter (for extra-nodal lesions) 8. Written informed consent 9. Able to comply with requirements of the protocol (including PET scans) 10. Agree and be able to use adequate contraception if required Previous inclusion criteria: 1. Histologically confirmed CD30 positive classical Hodgkin lymphoma 2. No previous treatment for classical Hodgkin lymphoma 3. Aged more than or equal to 16 years 4. Stages II (with B symptoms, extranodal disease, bulky disease, =3 sites of nodal involvement, fewer than 3 sites of nodal involvement but unsuitable for radiotherapy because of anatomical distribution or ESR =50 mm/h), III and IV classical Hodgkin lymphoma 5. Any of the following: At any age, standard chemotherapy considered inappropriate because: 5.1. Impaired cardiac function defined either by an ejection fraction of less than 50% assessed by echocardiogram or nuclear medicine scan (MUGA) 5.2. Left ventricular ejection fraction =50% measured by MUGA or echocardiography but in the presence of significant comorbidities or cardiac risk factors such as diabetes mellitus, hypertension, peripheral vascular disease, ischaemicheart disease, pr
Exclusion criteria
Exclusion criteria: Current inclusion criteria as of 18/05/2018: 1. Nodular lymphocyte predominant Hodgkin lymphoma 2. Grade 2 or worse peripheral neuropathy 3. Haemoglobin <90 g/l (transfusion allowed) 4. Unsupported neutrophil count <1.0 x 109/l and platelet count <100 x 109/l unless due to bone marrow infiltration by Hodgkin lymphoma demonstrated by trephine biopsy 5. Serum bilirubin more than 1.5 times upper limit normal unless due to Hodgkin lymphoma or Gilbert?s syndrome 6. Creatinine clearance < 30 ml/min (calculated by the modified Cockroft-Gault formula) unless due to Hodgkin lymphoma. Patients with an eGFR < 30 ml/min but a measured GFR by another method (e.g. EDTA) of 30ml/min or greater would be eligible 7. Pregnant or lactating women 8. Any other cancer diagnosis within the last 24 months – except for: 8.1. Appropriately treated superficial melanoma, basal cell carcinoma and squamous cell carcinoma of the skin 8.2. Appropriately treated cervical intra-epithelial neoplasia 8.3. In situ or organ confined prostate cancer not currently requiring therapy Previous cancers treated with curative intent and with no evidence of recurrence following a minimum of at least 2 years of follow-up are permitted. 9. The use of other investigational or anti-neoplastic agents within the previous 6 weeks or during the trial 10. Known to be HIV, Hep B positive (Hep B Core antibody positive allows inclusion providing surface / core antigen both negative) or Hep C positive (Hep C antibody positive allows inclusion providing PCR for viral RNA is negative) 11. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin 12. Known cerebral or meningeal involvement by Hodgkin Lymphoma 13. Symptoms or signs of progressive multifocal leukoencephalopathy (PML) 14. Any active systemic viral, bacterial, or fungal infection requiring intravenous antimicrobials within 2 weeks prior to registration 15. Evidence of current uncontrolled cardiovascular conditions, including unstable angina and NYHA grade IV heart failure 16. ECOG score 4 at time of registration Previous exclusion criteria: 1. Nodular lymphocyte predominant Hodgkin lymphoma 2. Grade 2 or worse peripheral neuropathy 3. Haemoglobin <9 g/dl (transfusion allowed) 4. Unsupported neutrophil count <1.0 x 109/l and platelet count <100 x 109/l unless due to bone marrow infiltration by Hodgkin lymphoma demonstrated by trephine biopsy 5. Serum bilirubin more than 1.5 times upper limit normal unless due to Hodgkin lymphoma or Gilbert?s syndrome 6. Creatinine clearance less than 30 ml/min (calculated by the modified CockroftGault formula, see appendix) unless due to Hodgkin lymphoma. Patients with a calculated GFR less than 30 ml/min but a GFR by EDTA clearance of 30 ml/min or greater would be eligible 7. Pregnant or lactating women 8. Concurrent metastatic or new diagnosis of malignancy within the last 24 months ? except appropriately treated superficial melanoma, basal cell
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 18/05/2018: Complete metabolic response rate (CMR) after 4 cycles of brentuximab vedotin defined as Deauville score of 1, 2 or 3 at PET 4; Timepoint(s): After 4 cycles (12 weeks) Previous primary outcome measure: Complete response rate (CR) after 4 cycles of brentuximab vedotin defined as Deauville score of 1, 2; Timepoint(s): After 4 cycles (12 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 18/05/2018: 1. Tolerability is defined in terms of absence of toxicities related to brentuximab vedotin quantified by the CTCAE v4 criteria and dose intensity. Dose intensity is defined as the total dose prescribed to each patient as a proportion of the planned protocol dose. Timepoint: 16 cycles 2. Overall objective response rate (ORR), including complete or partial response (CR/PR), after 4 cycles and 16 cycles of treatment with brentuximab vedotin according to the Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification; Timepoint: 4 and 16 cycles 3. Progression Free Survival (PFS) where progression is defined as the time from date of Cycle 1 Day 1 until documented progressive disease or death from any cause; Timepoint: censored at 2 years after day 1 cycle 1 4. Overall survival (OS) and cause of death. OS is defined as the time from Cycle 1 Day 1 to the date of death from any cause. Alive patients will be censored at their date of last follow-up. Timepoint: censored at 2 years after day 1 cycle 1 5. Deauville score after cycle 2 based on blinded PET2 scan, Timepoint: 2 cycles 6. Correlation of Deauville score after 2 cycles (blinded PET2) with Deauville score after 4 cycles (PET 4), response after 16 cycles, progression-free and overall survival, Timepoint: After 2, 4 and 16 Cycles, Progression or Death. 7. Co-morbidities satisfying eligibility criteria in the study population and documented throughout the study, Timepoint: During treatment and follow-up 8. CIRS-G profile in the study population assessed at baseline, Timepoint: Baseline 9. Any additional treatments administered following treatment with brentuximab vedotin (BV), Timepoint: In follow-up Previous secondary outcome measu | — |
Countries
United Kingdom
Contacts
Public ContactEszter Nagy
Outcome results
None listed