Condition category
Cancer
Date applied
16/10/2013
Date assigned
16/10/2013
Last edited
18/05/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Mrs Kathryn Paterson

ORCID ID

Contact details

Institute for Cancer Studies
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
k.r.paterson@bham.ac.uk

Type

Public

Additional contact

Ms Eszter Nagy

ORCID ID

Contact details

Haematology Team
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
+44 (0)121 371 7862
BREVITY@trials.bham.ac.uk

Additional identifiers

EudraCT number

2012-000214-11

ClinicalTrials.gov number

NCT02567851

Protocol/serial number

14703

Study information

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

Acronym

BREVITY

Study hypothesis

The aim of BREVITY is to assess the effectiveness of a new drug called brentuximab vedotin in patients with newly diagnosed Hodgkin’s 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

NRES committee East Midlands -– Derby; 18/06/2013, ref: 13/EM/0159

Study design

Non-randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

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

Phase

Phase II

Drug names

Brentuximab vedotin

Primary outcome measures

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 trial start date

10/02/2013

Overall trial end date

20/04/2018

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 30; UK Sample Size: 30

Participant 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 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

Recruitment start date

10/02/2014

Recruitment end date

20/10/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Christie Hospital
Manchester
M20 4BX
United Kingdom

Trial participating centre

Churchill Hospital
Oxford
OX3 7LE
United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
Glasgow
G12 0YN
United Kingdom

Trial participating centre

St James's University Hospital
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Trial participating centre

The Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Clatterbridge Cancer Centre
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Guy's Hospital
London
SE1 9RT
United Kingdom

Trial participating centre

Freeman Hospital
Newcastle upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Norfolk and Norwich University Hospital
Norwich
NR4 7UY
United Kingdom

Trial participating centre

University Hospital of Wales
Cardiff
CF14 4XW
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Leukaemia and Lymphoma Research

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Millennium: The Takeda Oncology Company (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Bloodwise

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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.