Acalabrutinib and Rituximab in Previously Untreated Mantle Cell Lymphoma
- Registration Number
- NCT05004064
- Lead Sponsor
- University College, London
- Brief Summary
This is a phase II, single-arm, open-label, multicentre study of acalabrutinib and rituximab for elderly or frail patients with previously untreated mantle cell lymphoma.
- Detailed Description
This is a Phase II, multicentre, single arm, open label pilot study to assess the safety and efficacy of acalabrutinib in combination with rituximab for previously untreated elderly frail mantle cell lymphoma patients.
48 patients will be recruited from 12 UK centres over 30 months.
Patients will receive acalabrutinib and rituximab for up to six cycles. The cycle length is 28 days. Specifically, patients will receive acalabrutinib, orally, at a dose of 100 mg twice daily for 28 days and rituximab 375 mg/m2 intravenously on day 1 (+/-3) of each cycle.\* Patients with any degree of response at the Week 12 (end of cycle 3) and Week 24 assessments (end of cycle 6) will continue with acalabrutinib monotherapy at a dose of 100 mg twice daily until disease progression, the development of unacceptable toxicity or any other reason (whichever occurs sooner).
\* Note: Acalabrutinib may be administered at a dose of 100 mg od po for cycle 1 day 1-7 at the local investigator's discretion. The dose should be escalated to full dose (100 mg bd) by day 8, cycle 1 if no toxicity is seen (see dose modification section). If a patient experiences toxicity during cycle 1 day 1-7 100 mg od po, the case must be discussed with the TMG to decide if acalabrutinib should continue. The CTC CARAMEL team should be contacted as soon as possible to arrange discussions with the TMG. Rituximab may be administered subcutaneously at a flat dose of 1400 mg from cycle 2 onwards following an intravenous dose of 375 mg/m2 in cycle 1. Consider splitting the first dose of rituximab at cycle 1 in the minority of MCL patients presenting with a white cell count of \>25 x 109/L. Consider splitting 25-50 mg/m2 on D1 and 325-350 mg/m2 on D2 of cycle 1 (to a total of 375 mg/m2 over D1/D2) according to investigator and site preference. Full dose 375 mg/m2 IV (or s/c equivalent) should be given in all patients from cycle 2 as a single dose.
All patients will be followed up for a minimum of 2 years following being registered into the trial. For patients that have been in follow-up for more than 2 years, annual survival and disease status follow-up will continue until the end of the trial.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 48
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Acalabrutinib and rituximab Rituximab Patients with untreated mantle cell lymphoma will receive acalabrutinib and rituximab for up to six cycles. Each cycle will comprise of acalabrutinib 100mg twice daily orally for 28 days and rituximab 375mg/m2 IV on day 1 (+/1 3 days) of every cycle. Acalabrutinib and rituximab Acalabrutinib Patients with untreated mantle cell lymphoma will receive acalabrutinib and rituximab for up to six cycles. Each cycle will comprise of acalabrutinib 100mg twice daily orally for 28 days and rituximab 375mg/m2 IV on day 1 (+/1 3 days) of every cycle.
- Primary Outcome Measures
Name Time Method Overall response rate 24 weeks To determine the efficacy of acalabrutinib in combination with rituximab in terms of disease response.
- Secondary Outcome Measures
Name Time Method Quality of life up to 24 months At baseline, week 12, week 24, month 12 and month 24 The EORTC QLQ-C30 will be used to measure participant-assessed quality of life
Incidence and frequency of grade 1-2 and 3+ adverse events seen in both treatment arms. Between the start of study treatment and 30 calendar days post last IMP administration. Safety and toxicity will be characterised in terms of adverse events as assessed by CTCAE v5.0. The incidence and frequency of adverse events during treatment and after treatment will be assessed.
Overall survival From the date of first dose of acalabrutinib until the date of death. Assessed up to 42 months. Overall survival measured from the date of first dose of acalabrutinib until the date of death from any cause.
Progression free survival From the date of first dose of acalabrutinib until the date of progression or death. Assessed up to 42 months. Progression free survival measured from the date of first dose of acalabrutinib until the date of first documented progression or date of death from any cause.
Trial Locations
- Locations (12)
The Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Royal Cornwall Hospital
🇬🇧Cornwall, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
St. Bartholomew's Hospital
🇬🇧London, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
The Christie Hospital
🇬🇧Manchester, United Kingdom
Norfolk and Norwich University Hospital
🇬🇧Norwich, United Kingdom
Cancer and Haematology Centre, Churchill Hospital
🇬🇧Oxford, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Royal Stoke Hospital
🇬🇧Stoke-on-Trent, United Kingdom
Clatterbridge Cancer Centre
🇬🇧Wirral, United Kingdom