A Phase 2 interventional study of Brentuximab Vedotin in Hodgkin Disease, sponsored by University of Birmingham. Completed at 12 sites in United Kingdom. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2018-05-11.
Sponsored by University of Birmingham · Phase 2, Interventional, and Treatment
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.
Stage 1 will recruit 20 patients. If at least patients 8 respond after the initial 4 cycles of SGN-35 a further 10 patients will be recruited to stage 2.
In all cases 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.
After baseline staging (including PET and CT scans (PET0 + CT0), performed on PET scanners approved for the purpose by The PET Imaging Centre at St Thomas'/Guy's), all eligible and consenting patients will receive an initial 4 cycles of brentuximab vedotin following which response and continuation of brentuximab vedotin will be assessed by PET (PET4) in the first instance. Patients achieving CMR (Deauville score 1-3) will continue treatment. Patients achieving PMR (Deauville score 4,5 with uptake less than baseline) will also continue treatment. Patients achieving NMR (Deauville score 4,5 with no change in uptake from baseline) or PMD (Deauville score 4,5 with increased intensity of uptake compared to baseline and/or new lesions consistent with lymphoma) will stop brentuximab vedotin and be considered for alternative therapy.
CT4 will be performed for future comparison with CT8, CT12 and CT 16 (to exclude Progressive Disease (PD) and to correlate metabolic and radiological responses) and to inform continued treatment. Patients not achieving Deauville score 1-3 at PET 4 will also have a PET scan at completion of treatment (after 16 cycles or earlier if brentuximab vedotin discontinued for reasons other than PD)
In addition an exploratory PET scan will be performed after 2 cycles of brentuximab vedotin (PET2); investigators will be blinded to the results of PET2 which will not influence patient management in any way. All PET scans will be centrally reviewed for QA purposes by The PET Imaging Centre at St Thomas'/Guy's, under the supervision of Sally Barrington and Mike O'Doherty, using the framework developed for the recently completed RAPID and RATHL trials. CT scans after 4 cycles and at the end of treatment may also be reviewed.
After the initial 4 cycles of brentuximab vedotin, subsequent treatment will be response adapted according to PET scan result the following schedule:
All patients who have not progressed irrespective of how many cycles of brentuximab vedotin received will be clinically assessed every 3 months and have a CT scan at months 3, 6, 9, 12. These scan may take place during therapy. During follow-up CT scans will be performed 15, 18, 24 and 36 months from the start of treatment. For those still alive and disease-free after 3 years following start of treatment, follow-up will be according to local practice but data recorded must include date of progressive disease, type of any subsequent therapies, date and cause of death.
For patients who progress at any time, follow-up will be according to local practice but data must be recorded for 5 years form the start of treatment and must include date of progressive disease, type of any subsequent therapies, date and cause of death.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 38 is close to the median of 40 across 4,508 interventional studies indexed under Lymphoma.
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Any of the following:
At any age and with ECOG score of 0, 1, 2 or 3, for whom standard chemotherapy considered inappropriate because:
For patients aged 60 years or older,
All co-morbidities must be documented on the baseline form and the CIRS-G score (if 60 years or older) recorded.
Exclusion Criteria:
Any other cancer diagnosis within the last 24 months - except for:
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.
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
Monoclonal antibody drug conjugate
Also known as: Adcetris
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.
Time frame: 4 cycles (3 months)
Tolerability is defined in terms of absence of toxicities related to BV quantified by the CTCAE v4 criteria and dose intensity.
Numbers of patients in each CTCAE toxicity category will be reported. Dose intensity will be reported as the median dose intensity together with full range. The number of patients with dose interruptions, dose reductions and number discontinuing treatment will also be reported over the treatment period.
Time frame: 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
ORR based on the Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification will be presented as the number of patients in each response category (CR/PR), as well as overall.
Time frame: 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
Survival estimates (PFS) will be calculated using the Kaplan-Meier method. Median, 12, 24 and 60 month estimates will be presented with CIs. Causes of death will also be reported.
Time frame: 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
Survival estimates (OS) will be calculated using the Kaplan-Meier method. Median, 12, 24 and 60 month estimates will be presented with CIs. Causes of death will also be reported.
Time frame: 5 years from start of treatment
Deauville score after cycle 2 based on blinded PET2 scan
Deauville score after cycle 2 (blinded PET2) will be reported as the number of patients in each score category. Scores will also be categorised into complete response (DS=1, 2 or 3) or not complete response (DS=4,5) and reported as the number and proportion of patients in each category
Time frame: 5 years from start of treatment
Correlation of Deauville score after 2 cycles (blinded PET2) with Deauville score after 4 cycles (PET 4)
Correlation coefficients will be reported to assess the association of DS after 2 cycles (at blinded PET2) with DS after 4 cycles (at PET 4) will be assessed by cox-regression modelling
Time frame: 5 years from start of treatment
Correlation of Deauville score after 2 cycles (blinded PET2) with response after 16 cycles
Correlation coefficients will be reported to assess the association of DS after 2 cycles (at blinded PET2) with end of treatment response. The relationship will also be assessed by cox-regression modelling
Time frame: 5 years from start of treatment
Correlation of Deauville score after 2 cycles (blinded PET2) with overall survival
Correlation coefficients will be reported to assess the association of DS after 2 cycles (at blinded PET2) with OS and also will be assessed by cox-regression modelling
Time frame: 5 years from start of treatment
Correlation of Deauville score after 2 cycles (blinded PET2) with progression-free survival
Correlation coefficients will be reported to assess the association of DS after 2 cycles (at blinded PET2) with PFS and assessed by cox-regression modelling
Time frame: 5 years from start of treatment
CIRS-G profile in the study population assessed at baseline
Numbers of patients in each CIRS-G score at baseline will be reported.
Time frame: 5 years from start of treatment
Co-morbidities satisfying eligibility criteria in the study population and documented throughout the study
Numbers of patients will be presented for common co-morbidities (ECOG and IPS) and any additional treatments administered following treatment with brentuximab vedotin
Time frame: 5 years from start of treatment
Differences in Progression Free Survival between patients who continue treatment following PET4 due to CMR and those who continue treatment following PMR at PET4.
Where appropriate secondary outcomes analysis will be repeated to explore differences between patients who continue treatment following PET4 due to CMR and those who continue treatment following PMR at PET4.
Time frame: 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.
Where appropriate secondary outcomes analysis will be repeated to explore differences between patients who continue treatment following PET4 due to CMR and those who continue treatment following PMR at PET4.
Time frame: 5 years from start of treatment
This study is completed, as verified in Nov 2017. You cannot join it, but the record below documents what was studied.
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University of Birmingham