ZEBRA Zanubrutinib plus rituximab (Zanu-R) as fixed duration, early intervention versus observation for patients with indolent mantle cell lymphoma: a randomised phase II clinical trial

Mantle cell lymphoma (MCL) is an uncommon type of non-Hodgkin lymphoma. Most patients with MCL need to start treatment soon after diagnosis, usually with a combination of chemotherapy and a 'targeted' treatment called rituximab. 25-30% of patients have 'indolent' (non-aggressive) MCL where the standard approach is an initial period of 'watchful waiting' followed by treatment with rituximab and chemotherapy when the lymphoma worsens (progresses).In this trial we will investigate whether there is a benefit of giving earlier treatment with zanubrutinib and rituximab (Zanu-R) compared to patients not being treated (watchful waiting). This is a randomised trial, meaning half of the patients with receive Zanu-R, and half will undergo 'watchful waiting' without any treatment.Patients who receive trial treatment will take zanubrutinib capsules twice a day, every day for six 28-day cycles and rituximab given as an infusion into a vein on or around the first day of each cycle. Patients who do not receive trial treatment will continue active observation (watch and wait) until clinical progression. Upon clinical progression all patients will be treated as per standard of care.All patients will be followed up for a minimum of 2 years following being enrolled into the trial until the last patient entering the trial completes their 2 year follow up visit.The trial will be conducted at NHS hospitals and is expected to last 4 ½ years.