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.~26 patients will be recruited from 12 UK centres over 18 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 (see dose modification section). 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 25mg/m2 on Day 1 and 350mg/m2 on Day 2 of cycle 1.~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.
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.