This clinical trial is for men and women who have mantle cell lymphoma, a sub-type of B-cell non-Hodgkin lymphoma, who have never received treatment for their disease before.

The purpose of this study is to learn more about the safety and effectiveness of the drug acalabrutinib when given in combination with the drugs venetoclax and rituximab (AVR) to participants with previously untreated mantle cell lymphoma (MCL). The use of acalabrutinib, venetoclax and rituximab to treat previously untreated MCL is experimental, which means it has not been fully tested yet and is not approved by the U.S. Food and Drug Administration (FDA).

Acalabrutinib and venetoclax are tablets, taken by mouth. Rituximab is a solution for intravenous infusion (meaning it is given directly into a vein via a small plastic tube called a catheter).

All study participants will receive the same combination of the three study drugs (AVR). The AVR combination will be given for 13 cycles. Each cycle will last 28 days (4 weeks). After the first 13 cycles of AVR, participants will have one additional cycle (Cycle 14) of acalabrutinib only while awaiting assessment results to see whether the treatment has been effective. After the assessment, if signs of a participant’s disease have disappeared and they have no residual disease (as evaluated by their study doctor), they will be randomly assigned to continue treatment with acalabrutinib (“acalabrutinib” group) or stop it (“observation” group).

Including post-treatment follow-up visits, participants will be in the study for up to 67 months (about 5 and a half years).