A Dose-Finding and Efficacy Study of Venetoclax, CC-486, and Obinutuzumab in Follicular Lymphoma

Exclusion Criteria

• •Participants are excluded from the study if any of the following criteria apply:
• •1. A a woman of childbearing potential who has a positive urine pregnancy test within 72 hours prior to treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for the subject to start receiving study medication.
• •2. Has received any prior systemic therapy other than anti-CD20 monoclonal antibody or radiotherapy prior to the first dose of study medication. Subjects must not have had a prior dose of anti-CD20 monoclonal antibody therapy within 28 days prior to the first dose of study medication.
• •3. Known hypersensitivity or allergy to any of the study drugs, xanthine oxidase inhibitors and/or rasburicase, mannitol, murine products, or any components of the drug formulations.
• •4. History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies.
• •5. History of other malignancy that could affect compliance with the study or interpretation of results such as:
• •* Participants with a history of basal or squamous cell carcinoma or stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible.
• •* Participants with a malignancy that has been treated with surgery alone with the intent to cure the participant will also be excluded. Individuals in documented remission without treatment for 2 years prior to enrollment may be included at the discretion of the doctor leading the study.
• •6. Has medical/clinical evidence of transformation to an aggressive lymphoma subtype including grade 3b Follicular Lymphoma.
• •7. Has received the following agents within 7 days prior to the first dose of venetoclax:
• •* Steroid therapy for anti-neoplastic intent
• •* A strong or moderate Cytochrome P450 3A (abbreviated as "CYP3A" inhibitor).
• •* CYP3A inducers
• •* Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax
• •* P-glycoprotein (P-gp) inhibitors or narrow therapeutic index P-gp substrates
• •8. Evidence of significant, uncontrolled diseases that could affect the participant's ability to fulfill their role in the study/ protocol or interpretation of results or that could increase risk to the participant, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm).
• •9. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1. Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment) will result in study exclusion. Caution should be exercised when considering the use of any of the study medication in participants with a history of recurring or chronic infections.
• •10. Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
• •11. Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody. Participants who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation. Participants with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV DNA is undetectable. These participants must be willing to undergo monthly HBV DNA testing.
• •12. Receipt of live-virus vaccines within 30 days prior to the initiation of study treatment
• •13. Malabsorption syndrome, inability to swallow a large number of pills, or other condition that precludes enteral route of administration.
• •14. A history of progressive multifocal leukoencephalopathy (PML) or known prior infection with the John Cunningham (JC) virus.
• •15. Significant active cardiac disease within the previous 6 months including New York Heart Association class 4 heart failure, unstable angina, or myocardial infarction.