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: 1. Subjects ≥ 18 years age and ≤ 80 years of age at the time of signing the informed consent form. 2. Understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. 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. 5. 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; 1\. CIRS ≥ 6; 2. Creatinine Clearance \< 70 mL/min; 3. Subject is not a candidate for a chemoimmunotherapy in the opinion of investigator. ii. Treatment with an approved BTK inhibitor is not required if subject has contraindications or is not a candidate for such a therapy in the opinion of the investigator. b. For Arm B, subjects with treatment-naïve or R/R CLL must meet the following criteria: i. Dose Escalation Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have either R/R CLL or treatment naïve (ie, first-line) CLL if the subject: 1. has 17p- and/or TP53 mutation; or 2. is unfit for standard chemoimmunotherapy meeting at least 1 of the following co-morbidity criteria: a. CIRS ≥ 6; b. Creatinine Clearance \< 70 mL/min; c. Subject is not a candidate for a chemoimmunotherapy in the opinion of the investigator. The reason for not being a candidate must be documented in CRF. ii. Dose Expansion Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have high risk CLL. High risk is defined as: 1) 17p- and/or TP53 mutation positive in treatment naïve CLL; or 2) 17p- and/or TP53 mutation positive, and/or complex karyotype, and/or progression \< 24 months after completion of 1st line chemoimmunotherapy in R/R CLL c. Subjects with R/R SLL or CLL with bulky disease (at least one lymph node measuring \> 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. 6\. Subjects must have the following lab values: 1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 or ≥ 1000 cells/mm3 if secondary to bone marrow involvement by disease. 2. 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. 3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) \< 3.0 x upper limit of normal (ULN) unless due to disease. 4. Serum bilirubin \< 1.5 x ULN unless due to Gilbert's syndrome. o Serum bilirubin ≤ 1.0 x ULN unless due to Gilbert's syndrome, Treatment Arm B only (CC-122 in combination with ibrutinib) 5. Calculated creatinine clearance of ≥ 60 ml/min. 6. No evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be enrolled upon correction of electrolyte abnormalities). 7\. ECOG PS (Eastern Cooperative Group Performance Status) of 0 or 1. 8. Ability to swallow oral capsules without difficulty. 9. Pregnancy Prevention Risk Management Plan: <!-- --> 1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. Other than the subject, FCBP and males should not handle the IP or touch the capsules, unless gloves are worn. 7. Be counseled about pregnancy precautions and risks of fetal exposure. ARM B ONLY: 10\. 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: 11\. Subjects in Cohort 2 of Arm C must meet the following criteria: 1. Subject must have received at least one BCR PI (ibrutinib, idelalisib, or other approved BTK or PI3K inhibitor) and/or venetoclax; 2. Subject must be either resistant to or intolerant of (ie., treatment failures) the last BCR PI and/or venetoclax. Resistant is defined as relapsed or refractory per IWCLL2008: i. Relapse is defined as a patient who has previously achieved a CR or PR, but after a period of 6 or more months, demonstrates evidence of disease progression. ii. Refractory is defined as failing to achieve a CR or PR, or disease progression within 6 months after initiation of treatment with an approved BTK or PI3K inhibitor (eg, ibrutinib, idelalisib) or venetoclax. iii. Intolerance is defined as the inability to continue treatment with a BCR PI or venetoclax due to toxicities or due to development of a contraindication that makes the subject ineligible to receive further treatment with a BCR PI or venetoclax. Exclusion Criteria: 1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 3. Any condition that confounds the ability to interpret data from the study. 4. Prior autologous or allogeneic stem cell transplant (SCT)/bone marrow transplant within 12 months of signing the ICD. Subjects who received allogeneic SCT ≥ 12 months before signing the ICD may be eligible provided there is no ongoing graft-versus-host disease and no ongoing immune suppression therapy. 5. Uncontrolled intercurrent illness including, but not limited to: 1. Ongoing or active infection requiring parenteral antibiotics. 2. Uncontrolled diabetes mellitus. i. The glycemic targets for subjects with diabetes should take into consideration age, comorbidities, life expectancy, and functional status of the subjects and follow established guidelines (eg, International Diabetes Federation, the European Diabetes Working Party guidelines, and the American Diabetes Association). For younger (\< 70 years old) or subjects with life expectancy ≥ 10 years, the target glycosylated hemoglobin, type A1C (HbA1c) should be \< 7.0%. The target HbA1c for older (≥ 70 years old) subjects or subjects with life expectancy \< 10 years should be \< 8.0%. Consultation with an endocrinologist is recommended when deciding if diabetes is optimally controlled. c. Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart Association Classification for Heart Disease). d. Active central nervous system involvement as documented by spinal fluid cytology or imaging. e. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia. f. Other concurrent severe and/or uncontrolled concomitant medical conditions that could cause unacceptable safety risks or compromise compliance with protocol. 6. History of second malignancies with life expectancy of \< 2 years or requirement of therapy that would confound study results. This does not include the following: 1. Basal cell carcinoma of the skin. 2. Squamous cell carcinoma of the skin. 3. Carcinoma in situ of the cervix. 4. Carcinoma in situ of the breast. 5. Carcinoma in situ of the bladder. 6. Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b). 7. Known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV), or hepatitis B or C virus (HBV, HCV). a. Hepatitis B screening is mandatory for all patients (HBsAg and anti-HBc). Patients with active hepatitis B disease should not be treated with obinutuzumab. Patients should be referred to a specialist if they are carriers before treatment starts (see PI or SmPC). Subjects who are positive for anti-HBc and/or anti-HBs but negative for HBsAg and HBV DNA may be treated after consultation with a hepatologist. 8. Any peripheral neuropathy ≥ NCI CTCAE Grade 2. 9. Use of systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day. 10. Medicines with high probability to cause QT prolongation or torsades de pointes. Subjects on chronic medications in this category may enroll after discussion with the medical monitor if changing these medications are not in the best medical interest of the patient. 11. History of hypersensitivity to IMiDs® (lenalidomide, pomalidomide, thalidomide). 12. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: 1. Left ventricular ejection fraction (LVEF) \< 45% as determined by MUGA scan or echocardiogram (ECHO). 2. Complete left bundle branch, or bifasicular, block. 3. Congenital long QT syndrome. 4. Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation. 5. QTcF \> 470 msec on Screening ECG (mean of triplicate recordings). 6. Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting CC 122. 7. Uncontrolled congestive heart failure or uncontrolled hypertension. 8. Troponin-T value \>0.4 ng/mL or BNP \>300 pg/mL. Subjects with baseline troponin-T \>ULN or BNP \>100 pg/mL are eligible but must have cardiologist evaluation prior to enrollment in the trial for baseline assessment and optimization of cardioprotective therapy. 13. Chemotherapy, radiotherapy, investigational anticancer therapy or major surgery within 28 days of Day 1 dosing with the following exceptions: a. Arm A: A minimum 5-day washout after discontinuation of ibrutinib therapy (or other BTK inhibitors) is required; only those subjects without rapid disease progression during the 5-day washout will be allowed to enroll into Arm A. i. Rapid disease progression is defined as follows: 1\. For subjects with measurable nodal disease, the increase in the sum of diameters of the largest lymph nodes (up to 3 nodes) exceeds 1 cm per day OR the diameter of the largest lymph node exceeds 5 cm during the 5 day wash out. 2. For subjects with lymphocytosis, the increase in the ALC exceeds 2x109/L per day OR the ALC exceeds 100,000 x109/L during the 5-day wash out; b. Arm C: No minimum washout is required after discontinuation of ibrutinib (or other BTK inhibitors) c. Approved PI3 kinase inhibitors: Subjects may start study treatment within 3 days of discontinuation of approved PI3 kinase inhibitors. 14\. Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management 15. Active disease transformation (ie, Richter's Syndrome); subjects with Richter's Syndrome that has resolved \> 2 years from signing the ICD are eligible. 16\. Known acute or chronic pancreatitis 17. Pregnant or lactating females Arm B only (CC-122 in combination with ibrutinib): 18\. Prior treatment with a BTK inhibitor 19. Presence of transfusion-dependent thrombocytopenia or a history of bleeding disorders or clinical conditions (eg, gastrointestinal bleeding or constitutional disorders) that may increase risk of life-threatening bleeding when thrombocytopenic 20. History of stroke or intracranial hemorrhage within 6 months prior to signing the ICD 21. Medications that are strong inhibitors or inducers of CYP3A4/5 (eg, itraconazole, ketoconazole, clarithromycin, ritonavir, phenytoin, pentobarbital, and rifampin) should be changed; subjects who cannot change these medications must be excluded. 22\. Use of concomitant anticoagulation with warfarin or other vitamin K antagonists is prohibited, as is treatment with these agents in the 7 days prior to signing the ICD. The use of other anticoagulants (eg, heparins) and anti-platelet agents is allowed per investigator's discretion. Arm C only (CC-122 in combination with obinutuzumab): 23\. Hypersensitivity to obinutuzumab