Hodgkin lymphoma MedDRA version: 16.1 Level: LLT Classification code 10020261 Term: Hodgkin's disease NOS stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 16.1 Level: PT Classification code 10020270 Term: Hodgkin's disease stage III System Organ Class: 10029104
Conditions
Interventions
Trade Name: Adcetris
Product Name: Brentuximab vedotin
Product Code: SGN-35
Pharmaceutical Form: Powder for solution for injection
INN o
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
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: a. Impaired cardiac function defined either by an ejection fraction of less than 50% assessed by echocardiogram or nuclear medicine scan (MUGA) b. Left ventricular ejection fraction =50% measured by MUGA or echocardiography but in the presence of significant co-morbidities or cardiac risk factors such as diabetes mellitus, hypertension, peripheral vascular disease, ischaemic heart disease, previous myocardial infarction, obesity, stroke or transient ischaemic attacks (TIA) that make anthracycline-containing chemotherapy inadvisable as determined by the treating physician. c.Heart failure clinically determined by the presence of New York Heart Association (NYHA) heart failure grade II and III due to a cause other than HL d.Impaired respiratory function with DLCO and/or FVC/FEV1 ratio less than 75% of predicted due to a cause other than HL For patients aged 60 years or older, e. an ECOG score of 1, 2 or 3 for any reason, before the start of permitted steroids and considered unsuitable for treatment with standard chemotherapy by the supervising physician. 6. FDG avid disease 7. Measurable disease with at least one lesion measuring 1.5 cm in short axis diameter 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 Are the trial subjects under 18? yes Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 4 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
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 10-9/l and platelet count <100 x 10-9/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, see appendix) unless due to Hodgkin lymphoma. Patients with an eGFR < 30 ml/min but a measured GFR by other method (e.g. EDTA) of 30ml/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 carcinoma and squamous cell carcinoma of the skin, cervical intra-epithelial neoplasia or in situ or organ confined prostate cancer not currently requiring therapy 9. The use of other investigational or anti-neoplastic agents within the previous 6 weeks or during the trial. Corticosteroids are allowable for immediate relief of symptoms 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 PML 14. Any active systemic viral, bacterial, or fungal infection requiring intravenous antibiotics within 2 weeks prior to cycle 1 day 1 of brentuximab vedotin 15. Evidence of current uncontrolled cardiovascular conditions, including unstable angina and NYHA grade IV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • Determine tolerability in terms of toxicity, number of doses of brentuximab vedotin administered, dose reductions and treatment delays. • How many patients have a positive response after 4 cycles using a different response criteria called the revised response criteria • Determine how long patients survive without disease progression • Determine the overall survival and cause of death in these patients • How many patients have a positive response after 2 cycles, using a blinded PET CT scan • To determine if you can predict positive responses earlier in treatment by correlating responses after 2 cycles (blinded PET) to the responses after 4 cycles, and of end treatment, progression free and over all survival • Assess the profile of co-morbidities in the patient group • Collate reported performance status using the CIRS-R score • Collate information on alternative and additional treatments administered following treatment with brentuximab vedotinin ;Main Objective: To determine how many patients treated with 4 cycles of brentuximab vedotin, who are unsuitable for conventional chemotherapy, have a complete response to the treatment (as measured by PET scan Deauville score 1,2 or 3). ;Primary end point(s): Complete response rate after 4 cycles (12 weeks) of brentuximab vedotin defined as Deauville score of 1, 2 or 3 by PET 4;Timepoint(s) of evaluation of this end point: after 4 cycles of treatment (12 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Tolerability and dose intensity • Overall objective response rate (ORR), including complete or partial response (CR/PR), after 4 cycles of treatment with brentuximab vedotin according to the Revised Response Criteria for malignant lymphoma • Progression Free Survival (PFS) where progression is defined according to the Revised Response Criteria for malignant lymphoma • Overall survival (OS) and cause of death • Deauville score after cycle 2 based on blinded PET2 scan • Correlation of Deauville score after 2 cycles (blinded PET2) with Deauville score after 4 cycles (PET 4), end of treatment response, progression-free and overall survival • Co-morbidity profile in the study population documented throughout the study • CIRS-G profile in the study population assessed at baseline • Any additional treatments administered following treatment with brentuximab vedotin ; Timepoint(s) of evaluation of this end point: 16 cycles of brnetuximab (48 weeks) for the Tolerability/dose intensity. 4 cycles (12 weeks)for the ORR endpoints. 5 years for the PFS and OS endpoints and for correlation with the blinded PET. 2 cycles (6 weeks) for the Deuville score following PET 2. Study entry for the co-morbidity and CIRS-G assessments. 5 years for the additional treatments. | — |
Countries
United Kingdom
Contacts
Public ContactKathryn Paterson
University of Birmingham
Outcome results
None listed