Brentuximab vedotin In patients with Hodgkin lymphoma
| ISRCTN | ISRCTN77650947 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77650947 |
| EudraCT/CTIS number | 2012-000214-11 |
| ClinicalTrials.gov number | NCT02567851 |
| Secondary identifying numbers | 14703 |
- Submission date
- 16/10/2013
- Registration date
- 16/10/2013
- Last edited
- 28/05/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Ms Eszter Nagy
Public
Public
Haematology Team
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
| Phone | +44 (0)121 371 7862 |
|---|---|
| BREVITY@trials.bham.ac.uk |
Study information
| Study design | Non-randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | BREVITY: A phase II study of brentuximab vedotin using a response adapted design in patients with Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or co-morbidity |
| Study acronym | BREVITY |
| Study objectives | The aim of BREVITY is to assess the effectiveness of a new drug called brentuximab vedotin in patients with newly diagnosed Hodgkins Lymphoma for whom standard chemotherapy is not considered a good option due to age or frailty. Brentuximab vedotin is a new type of drug known as an antibody-drug conjugate and is made up of 2 parts linked together, an anti-body and a chemotherapy drug. The antibody acts like a homing device, and takes the chemotherapy drug directly to the lymphoma cells, where it causes them to die when they try to divide. |
| Ethics approval(s) | NRES committee East Midlands - Derby; 18/06/2013, ref: 13/EM/0159 |
| Health condition(s) or problem(s) studied | Topic: National Cancer Research Network; Subtopic: Lymphoma; Disease: Lymphoma (Hodgkin's) |
| Intervention | 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. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Brentuximab vedotin |
| Primary outcome measure | 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 outcome measures | 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 measures: 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: 4 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 Revised Response Criteria for malignant lymphoma. Timepoint: 4 and 16 cycles 3. Progression Free Survival (PFS) where progression is defined according to the Revised Response Criteria for malignant lymphoma [4] is defined as the time from date of Cycle 1 Day 1 until documented progressive disease or death from any cause. Timepoint: censored at 5 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 5 years after day 1 cycle 1 5. Deauville score after cycle 2 based on blinded PET2 scan, Timepoint: 2 cycle 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 |
| Overall study start date | 10/02/2013 |
| Completion date | 20/04/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 30; UK Sample Size: 30 |
| Total final enrolment | 38 |
| Key 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 < 50% assessed by echocardiogram or nuclear medicine scan (MUGA) 5.2. Left ventricular ejection fraction more than or equal to 50% measured by echocardiography or MUGA 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 investigator. 5.3. 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 Hodgkin lymphoma 5.4. Impaired respiratory function with DLCO and/or FVC/FEV1 ratio <75% of predicted due to a cause other than Hodgkin lymphoma 5.5. For patients aged 60 years or older, an ECOG score of 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 – proven by PET scan 7. Measurable disease with at least one lesion measuring >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, previous myocardial infarction, obesity, stroke or transient ischaemic attacks (TIA) that make anthracyclinecontaining chemotherapy inadvisable as determined by the treating physician. 5.3. 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 5.4.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, 5.5. an ECOG score of 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 |
| Key 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 Gilberts 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 Gilberts 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 carcinoma and squamous cell carcinoma of the skin, cervical intraepithelial neoplasia or in situ or organ confined prostate cancer not currently requiring therapy 9. The use of other investigational or antineoplastic 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 or C positive 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 |
| Date of first enrolment | 10/02/2014 |
| Date of final enrolment | 20/10/2017 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Christie Hospital
Manchester
M20 4BX
United Kingdom
M20 4BX
United Kingdom
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
OX3 7LE
United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow
G12 0YN
United Kingdom
G12 0YN
United Kingdom
St James's University Hospital
Leeds
LS9 7TF
United Kingdom
LS9 7TF
United Kingdom
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
SO16 6YD
United Kingdom
The Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom
NG5 1PB
United Kingdom
Clatterbridge Cancer Centre
Liverpool
L7 8XP
United Kingdom
L7 8XP
United Kingdom
Guy's Hospital
London
SE1 9RT
United Kingdom
SE1 9RT
United Kingdom
Freeman Hospital
Newcastle upon Tyne
NE7 7DN
United Kingdom
NE7 7DN
United Kingdom
Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom
LE1 5WW
United Kingdom
Norfolk and Norwich University Hospital
Norwich
NR4 7UY
United Kingdom
NR4 7UY
United Kingdom
University Hospital of Wales
Cardiff
CF14 4XW
United Kingdom
CF14 4XW
United Kingdom
Sponsor information
University of Birmingham (UK)
University/education
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Charity
Leukaemia and Lymphoma Research
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Millennium: The Takeda Oncology Company (USA)
No information available
Bloodwise
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | results presented at 14th International Conference on Malignant Lymphoma Palazzo dei Congressi, Lugano (Switzerland): | 01/06/2017 | 07/06/2019 | No | No |
| Basic results | 28/05/2020 | No | No | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
28/05/2020: Added clinicaltrialsregister.eu link to basic results (scientific).
07/06/2019: Publication reference and total final enrolment added.
22/05/2019: Contact details updated.
18/05/2018: The following changes have been made:
1. The clinicaltrials.gov number has been added.
2. The primary outcome measure has been changed.
3. The secondary outcome measures have been changed.
4. The overall start date has been changed from 28/10/2013 to 10/02/2013.
5. The overall trial end date has been changed from 21/08/2015 to 20/04/2018.
6. The participant inclusion criteria have been changed.
7. The participant exclusion criteria have been changed.
8. The recruitment start date has been changed from 28/10/2013 to 10/02/2014.
9. The recruitment end date has been changed from 21/08/2015 to 20/10/2017.
10. Leukaemia and Lymphoma Research has been replaced as a funder by Bloodwise.
11. The University of Birmingham has been removed as a trial centre and Christie Hospital, Churchill Hospital, Beatson West of Scotland Cancer Centre, St James's University Hospital, Southampton General Hospital, The Queen Elizabeth Hospital, Nottingham City Hospital, Clatterbridge Cancer Centre, Guy's Hospital, Freeman Hospital, Leicester Royal Infirmary, Norfolk and Norwich University Hospital, and University Hospital of Wales have been added.
14/09/2017: No publications found, verifying study status with principal investigator.
