Condition category
Cancer
Date applied
16/10/2013
Date assigned
16/10/2013
Last edited
14/08/2014
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

Additional identifiers

EudraCT number

2012-000214-11

ClinicalTrials.gov number

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; 18th June 2013; 13/EM/0159

Study design

Non-randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

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

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

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

28/10/2013

Overall trial end date

21/08/2015

Reason abandoned

Eligibility

Participant 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
Target Gender: Male & Female

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 30; UK Sample Size: 30

Participant 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

28/10/2013

Recruitment end date

21/08/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Institute for Cancer Studies
Birmingham
B15 2TT
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 & Lymphoma Research (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Millennium: The Takeda Oncology Company (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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