A Study of Brentuximab Vedotin in Patients With Hodgkin Lymphoma Unsuitable for Chemotherapy Due to Age, Frailty or Co-morbidity — BREVITY  

Hodgkin Disease Clinical Trial

Official 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

Status Completed

Clinical Trial 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.

Clinical Trial Description

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:

• Those with a Complete Metabolic Response (CMR, Deauville Score 1, 2 or 3) at PET 4 will receive up to 12 additional cycles of brentuximab vedotin (maximum of 16 cycles) depending on no evidence of PD by a CT scan performed after each group of 4 cycles of brentuximab vedotin.

• Patients with a Partial Metabolic Response (PMR) at PET4 will receive up to 12 additional cycles of brentuximab vedotin (maximum of 16 cycles) depending on no evidence of PD on a CT scan performed after each group of 4 cycles of brentuximab vedotin.

• Patients with No Metabolic Response (NMR) will stop brentuximab vedotin and be considered for alternative therapy.

• Patients with progressive disease at any time as determined by either CT or PET scan performed after each group of 4 cycles of brentuximab vedotin or in response to clinical concerns will stop study treatment and receive subsequent therapy at investigator discretion. Clinical concerns over PD should be confirmed by either a CT or PET scan.

• Patients who come off treatment with brentuximab vedotin for any other reason (toxicity, patient decision, investigator advice) should have a CT scan performed for response assessment. In addition patients with Partial Metabolic Response at PET 4 should also have a PET scan performed.

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. ;

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

• NCT number: NCT02567851
• Study type: Interventional
• Source: University of Birmingham
• Status: Completed
• Phase: Phase 2
• Start date: February 2014
• Completion date: October 2, 2017