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

Prior treatment

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

Other illness

• Subject has an uncontrolled infection
• Subject has HIV infection

Lab values

• All subjects will be screened for Hepatitis B (HBsAg, anti-HBs, anti-HBc IgM and total) and Hepatitis C (antibody or RNA). Subjects who are positive for Hepatitis B by 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 be required to undergo monthly HBV DNA testing and liver function liver function testing (AST, ALT, alkaline phosphatase, total bilirubin). Patients with HCV antibody positivity and HCV pcr negativity are eligible to be included.

Other

• 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 requires the use of warfarin
• A female subject is pregnant or breast-feeding

• Subjects must have a histologically confirmed diagnosis of mantle cell lymphoma as defined by the World Health Organization (WHO) classification scheme.
• Age ≥ 60
• Subjects must be previously untreated for mantle cell lymphoma and deemed to require treatment 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 transfusion within 14 days of Screening)
  • Hemoglobin ≥ 9.0 g/dL * These criteria may be waived by study investigators if there is evidence of bone marrow involvement by MCL that is believed to be the cause of the cytopenias.
• Subject must have adequate renal, and hepatic function, per laboratory reference range at screening as follows:
  • Subject must have adequate renal, and hepatic function, per laboratory reference range at screening as follows:
  • Calculated creatinine clearance ≥ 40 mL/min; determined via the Cockcroft-Gault formula.
  • AST and ALT ≤ 3.0 × ULN; Bilirubin ≤ 1.5 × ULN*. Subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN
  • These criteria may be waived by study investigators if abnormal values believed to be due to lymphoma.
• Female subjects must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a pregnancy test performed as follows:
  • At Screening on a serum sample obtained within 14 days prior to the first study drug administration, and
  • Prior to dosing on a urine sample obtained on Cycle 1 Day 1 if it has been > 7 days since obtaining the serum pregnancy test results.
  • All female subjects not surgically sterile or postmenopausal (for at least 1 year) and non-vasectomized male subjects must practice at least 1 of the following methods of birth control:
  • Total abstinence from sexual intercourse (minimum 1 complete menstrual cycle);
  • A vasectomized partner(s);
  • Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 3 months prior to study drug administration;
  • Double-barrier method (condoms and diaphragm with spermicidal [sponge, jellies or creams]).
• Ability to understand and willingness to sign IRB-approved informed consent