NCT02567851

Brief Summary

An early phase II, single arm, two stage study, to investigate the level of activity, duration of response and tolerability of brentuximab vedotin (SGN-35), as a single agent, utilising a response adapted approach, in older, frailer or co-morbid patients with previously untreated Hodgkin lymphoma. Opened Feb 2014 and will recruit over 18 months. Duration of treatment will be dependent on the patients' response (see schema below) with a maximum of 16 cycles over 48 weeks. At the end of treatment patients will be assessed clinically at 3 months intervals and by CT scan at 15, 18, 24 and 36 months. For those still alive and disease free after 2 years, follow-up will be according to local practice.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Feb 2014

Typical duration for phase_2

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2014

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

September 29, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 5, 2015

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 14, 2016

Completed
1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 2, 2017

Completed
Last Updated

May 11, 2018

Status Verified

November 1, 2017

Enrollment Period

2 years

First QC Date

September 29, 2015

Last Update Submit

May 9, 2018

Conditions

Hodgkin Disease

Keywords

Brentuximab VedotinPET scansLymphoma

Outcome Measures

Primary Outcomes (1)

  • Complete metabolic response rate (CMR) after 4 cycles of brentuximab vedotin defined as Deauville score of 1, 2 or 3 by PET

    The number of patients achieving a CR at PET4 (after cycle 4) with confidence intervals (CIs) will be presented and assessed using the Simons 2-stage design criterion.

    4 cycles (3 months)

Secondary Outcomes (11)

  • Tolerability is defined in terms of absence of toxicities related to BV quantified by the CTCAE v4 criteria and dose intensity.

    16 cycles (1 year from start of treatment)

  • Overall objective response rate (ORR), including complete or partial metabolic response (CMR/PMR), after 4 cycles and 16 cycles of treatment with BV according to The Lugano Classification

    16 cycles (1 year from start of treatment)

  • 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

    5 years from start of treatment

  • 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

    5 years from start of treatment

  • Deauville score after cycle 2 based on blinded PET2 scan

    5 years from start of treatment

  • +6 more secondary outcomes

Other Outcomes (2)

  • Differences in Progression Free Survival between patients who continue treatment following PET4 due to CMR and those who continue treatment following PMR at PET4.

    5 years from start of treatment

  • Differences in Overall Survival between patients who continue treatment following PET4 due to CMR and those who continue treatment following PMR at PET4.

    5 years from start of treatment

Study Arms (1)

Brentuximab Vedotin

EXPERIMENTAL

brentuximab vedotin will be administered at an initial dose of 1.8 mg/kg every 3 weeks as a 30-minute outpatient i.v. infusion. A maximum of 16 cycles

Drug: Brentuximab Vedotin

Interventions

Brentuximab VedotinDRUG

Monoclonal antibody drug conjugate

Also known as: Adcetris
Brentuximab Vedotin

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed CD30 positive classical Hodgkin lymphoma
  • No previous treatment for classical Hodgkin lymphoma
  • Aged ≥ 16 years
  • 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
  • Any of the following:
  • At any age and with ECOG score of 0, 1, 2 or 3, for whom standard chemotherapy considered inappropriate because:
  • Impaired cardiac function defined either by an ejection fraction of \< 50% assessed by echocardiogram or nuclear medicine scan (MUGA)
  • Left ventricular ejection fraction ≥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.
  • 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
  • Impaired respiratory function with DLCO and/or FVC/FEV1 ratio \<75% of predicted due to a cause other than Hodgkin lymphoma
  • For patients aged 60 years or older,
  • an ECOG score of 1, 2 or 3 for any reason, before the start of permitted steroids (see section 7.9) and considered unsuitable for treatment with standard chemotherapy by the investigator
  • All co-morbidities must be documented on the baseline form and the CIRS-G score (if 60 years or older) recorded.
  • FDG avid disease - proven by PET scan
  • 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)
  • +3 more criteria

You may not qualify if:

  • Nodular lymphocyte predominant Hodgkin lymphoma
  • Grade 2 or worse peripheral neuropathy
  • Haemoglobin \<90 g/L (transfusion allowed)
  • 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
  • Serum bilirubin ≥1.5 times upper limit normal unless due to Hodgkin lymphoma or Gilbert's syndrome
  • 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 another method (e.g. EDTA) of 30ml/min or greater would be eligible.
  • Pregnant or lactating women
  • Any other cancer diagnosis within the last 24 months - except for:
  • Appropriately treated superficial melanoma, basal cell carcinoma and squamous cell carcinoma of the skin
  • Appropriately treated cervical intra-epithelial neoplasia
  • 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.
  • The use of other investigational or anti-neoplastic agents within the previous 6 weeks or during the trial.
  • Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin.
  • Known cerebral or meningeal involvement by Hodgkin lymphoma
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

Beatson West of Scotland Cancer Center

Glasgow, United Kingdom

Location

St James University Hospital

Leeds, United Kingdom

Location

University Hospital

Leicester, United Kingdom

Location

Royal Liverpool Hospital

Liverpool, United Kingdom

Location

Guys Hospital

London, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

The Freeman Hospital

Newcastle, United Kingdom

Location

Norfolk and Norwich Hospital

Norwich, United Kingdom

Location

The Churchill Hospital

Oxford, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (1)

  • Gibb A, Pirrie SJ, Linton K, Warbey V, Paterson K, Davies AJ, Collins GP, Menne T, McKay P, Fields PA, Miall FM, Nagy E, Wheatley K, Reed R, Baricevic-Jones I, Barrington S, Radford J. Results of a UK National Cancer Research Institute Phase II study of brentuximab vedotin using a response-adapted design in the first-line treatment of patients with classical Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or comorbidity (BREVITY). Br J Haematol. 2021 Apr;193(1):63-71. doi: 10.1111/bjh.17073. Epub 2020 Sep 14.

    PMID: 32926420DERIVED

MeSH Terms

Conditions

Hodgkin DiseaseLymphoma

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

OligopeptidesPeptidesAmino Acids, Peptides, and ProteinsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulins

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 29, 2015

First Posted

October 5, 2015

Study Start

February 1, 2014

Primary Completion

January 14, 2016

Study Completion

October 2, 2017

Last Updated

May 11, 2018

Record last verified: 2017-11

Locations

GB(12)