Phase II Trial of Venetoclax and Rituximab as Initial Therapy in Older Patients With Mantle Cell Lymphoma

Inclusion Criteria:

• Subjects must have a histologically confirmed diagnosis of mantle cell lymphoma asdefined by the World Health Organization (WHO) classification scheme.

• Age ≥ 60

• Subjects must be previously untreated for mantle cell lymphoma and deemed to requiretreatment by the treating physician

• ECOG performance status of 0-3

• Subject must have adequate bone marrow* without growth factor support as follows:

• Absolute Neutrophil Count (ANC) ≥ 1000/μL

• Platelets ≥ 75,000/mm3 (entry platelet count must be independent of transfusionwithin 14 days of Screening)

• Hemoglobin ≥ 9.0 g/dL * These criteria may be waived by study investigators ifthere is evidence of bone marrow involvement by MCL that is believed to be thecause of the cytopenias.

• Subject must have adequate renal, and hepatic function, per laboratory referencerange at screening as follows:

• Subject must have adequate renal, and hepatic function, per laboratoryreference range at screening as follows:

• Calculated creatinine clearance ≥ 40 mL/min; determined via the Cockcroft-Gaultformula.

• AST and ALT ≤ 3.0 × ULN; Bilirubin ≤ 1.5 × ULN*. Subjects with Gilbert'sSyndrome may have a bilirubin > 1.5 × ULN

• These criteria may be waived by study investigators if abnormal valuesbelieved to be due to lymphoma.

• Female subjects must be surgically sterile, postmenopausal (for at least 1 year), orhave negative results for a pregnancy test performed as follows:

• At Screening on a serum sample obtained within 14 days prior to the first studydrug administration, and

• Prior to dosing on a urine sample obtained on Cycle 1 Day 1 if it has been > 7days since obtaining the serum pregnancy test results.

• All female subjects not surgically sterile or postmenopausal (for at least 1year) and non-vasectomized male subjects must practice at least 1 of thefollowing methods of birth control:

1. Total abstinence from sexual intercourse (minimum 1 complete menstrualcycle);
2. A vasectomized partner(s);
3. Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal)for at least 3 months prior to study drug administration;
4. Double-barrier method (condoms and diaphragm with spermicidal [sponge,jellies or creams]).

• Ability to understand and willingness to sign IRB-approved informed consent

Exclusion Criteria:

• Subject has blastoid-variant mantle cell lymphoma

• Subject requires immediate cytoreduction as determined by study investigators

• Subject has documented CNS involvement of mantle cell lymphoma

• Subject has Ann Arbor stage I or contiguous stage II mantle cell lymphoma

• Subject has an uncontrolled infection

• Subject has HIV infection

• All subjects will be screened for Hepatitis B (HBsAg, anti-HBs, anti-HBc IgM andtotal) and Hepatitis C (antibody or RNA). Subjects who are positive for Hepatitis Bby HBsAg or DNA as well as subjects positive for Hepatitis C will be excluded.Subjects with anti-HBc positivity and DNA negative may be included but will berequired to undergo monthly HBV DNA testing and liver function liver functiontesting (AST, ALT, alkaline phosphatase, total bilirubin). Patients with HCVantibody positivity and HCV pcr negativity are eligible to be included.

• Subject requires the use of warfarin

• Subject has received immunization with live virus vaccine within 28 days prior tothe first dose of study drug

• A female subject is pregnant or breast-feeding