The purpose of this study is to determine if giving an experimental drug called venetoclax in combination with lenalidomide and rituximab is safe and effective for treating people with Mantle Cell Lymphoma (MCL).

Inclusion Criteria:

• Age ≥18 years
• Diagnosis of mantle cell lymphoma (MCL) established by histologic assessment
• Laboratory, radiographic, physical exam findings and/or symptoms attributable to MCL
• ECOG Performance Status (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death) less or equal to 2
• All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program
• Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
• Men and Women of childbearing potential on appropriate contraception
• Adequate organ function
• Ability to understand and the willingness to sign a written informed consent.
• Ability to swallow oral capsules/tablets

Exclusion Criteria:

• Prior treatment for MCL with chemotherapy
• Pregnant or breastfeeding women
• Grade 2 or higher peripheral neuropathy
• Known history of CNS (Central Nervous System) or leptomeningeal by MCL prior to study enrollment
• Significant cardiovascular disease
• Any condition that might significantly impair drug absorption as determined by the investigator
• Uncontrolled active systemic fungal, bacterial, viral, or other infection, or intravenous anti-infective treatment within 2 weeks before first dose of study drug
• History of stroke or intracranial hemorrhage within 6 months of 1st dose of study drug
• Concurrent participation in another clinical trial
• Subject has received a moderate or strong CYP3A inhibitor or inducer within 1 week prior to treatment initiation.
• Psychiatric illness or social situations that would limit compliance with study requirements
• Subject has known positivity to HIV
• Active infection with Hepatitis B or C virus as determined by a detectable viral load on PCR.
• Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to< 2 years.