A Phase 1/2, Open-label, Dose Finding Study to Evaluate CC-122 in Combination With Ibrutinib and Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Inclusion Criteria

• Subjects ≥ 18 years age and ≤ 80 years of age at the time of signing the informed consent form.
• Understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
• Able to adhere to the study visit schedule and other protocol requirements.
• Must have a documented diagnosis of CLL/ SLL requiring treatment (per IWCLL guidelines). In addition:

a. Presence of at least one clinically measurable lesion: i. nodal lesion that measures ≥ 1.5 cm in longest dimension (LD) and ≥ 1.0 cm in longest perpendicular dimension (LPD), or ii. spleen that measures ≥ 14 cm in longest vertical dimension (LVD) with a minimum of 2 cm enlargement, or iii. liver that measures ≥ 20 cm in LVD with a minimum of 2 cm enlargement, or iv. peripheral blood B lymphocyte count > 5000/uL.

• Must meet the criteria for relapsed and/or refractory disease according to the IWCLL guidelines (Hallek, 2008) to ≥ 1 prior treatment (with the exception of Arm B) and have evidence of disease progression requiring treatment at the time of study entry as follows:

a. For Arms A and C, subjects must have received either prior chemoimmunotherapy or therapy with an approved BTK inhibitor with the following exceptions: i. Chemoimmunotherapy is not required if subjects have specific comorbidities that preclude the use of standard chemoimmunotherapy meeting at least 1 of the following criteria;

• CIRS ≥ 6; 2. Creatinine Clearance 5.0 cm in diameter) are considered at higher risk for developing a TFR and may only be enrolled upon discussion with the sponsor's medical monitor and agreement to close medical management.
• Subjects must have the following lab values:
• Absolute neutrophil count (ANC) ≥ 1, 500 cells/mm3 or ≥ 1000 cells/mm3 if secondary to bone marrow involvement by disease.
• Platelet count ≥ 100, 000 cells/mm3 (100 x 109/L) or ≥ 50,000 cells/mm3 (50 x 109/L) if secondary to bone marrow involvement by disease.
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT)
• Females of childbearing potential (FCBP) must undergo pregnancy testing based on the frequency outlined in the Pregnancy Prevention Risk Management Plan (PPRMP) and pregnancy results must be negative.
• Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods as specified in the PPRMP.

*For Arm C, subjects must agree to use adequate contraceptive methods for 18 months (please refer to the obinutuzumab IB, PI, and SmPC).

• Complete abstinence is only acceptable in cases where this is the preferred and usual lifestyle of the subject.
• Periodic abstinence (calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable.
• Males (including those who have had a vasectomy) must practice complete abstinence or use barrier contraception (condoms) when engaging in sexual activity with FCBP as specified in the PPRMP.
• Males must agree not to donate semen or sperm for the duration of the study and for 3 months after the last dose of CC-122.
• All subjects must:
• Understand that the (investigational Product) IP could have a potential teratogenic risk.
• Agree to abstain from donating blood while taking IP and following discontinuation of IP.
• Agree not to share IP with another person.
• Other than the subject, FCBP and males should not handle the IP or touch the capsules, unless gloves are worn.
• Be counseled about pregnancy precautions and risks of fetal exposure.

ARM B ONLY:

• Enrollment into Arm B will be permitted if ibrutinib is considered the standard of care in the clinical practice.

EXPANSION COHORT 2 OF ARM C:

• Subjects in Cohort 2 of Arm C must meet the following criteria:
• Subject must have received at least one BCR PI (ibrutinib, idelalisib, or other approved BTK or PI3K inhibitor) and/or venetoclax;
• Subject must be either resistant to or intolerant of (