Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Multi-center, Open-label, Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Brief Summary: The primary objective of this study is to evaluate the efficacy of ibrutinib in combination with obinutuzumab compared to chlorambucil in combination with obinutuzumab based on the Independent Review Committee (IRC) assessment of progression free survival (PFS). Efficacy will be evaluated according to 2008 International Workshop for Chronic Lymphocytic Leukemia (IWCLL) criteria with the modification for treatment-related lymphocytosis, in subjects with treatment-naive CLL or SLL.


Options:
A: Inclusion Criteria:

Disease Related:

1. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria.
2. Age 65 yrs and older OR if less than 65 years, must have at least one of the following criteria:

   * Cumulative Illness Rating Score (CIRS) \>6
   * Creatinine clearance estimated \<70 mL/min using Cockcroft-Gault equation.
   * Del 17p by fluorescence in situ hybridization (FISH) or TP53 mutation by polymerase chain reaction (PCR) or Next Generation Sequencing
3. Active disease meeting at least 1 of the following IWCLL criteria for requiring treatment:

   * Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and thrombocytopenia
   * Massive, progressive, or symptomatic splenomegaly
   * Massive nodes (at least 10 cm longest diameter), or progressive or symptomatic lymphadenopathy.
   * Progressive lymphocytosis with an increase of more than 50 percent over a 2-month period or a lymphocyte doubling time (LDT) of \<6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of \<30,000/µL, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
   * Autoimmune hemolytic anemia and/or immune thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy.
   * Autoimmune hemolytic anemia is defined by at least one marker of hemolysis (indirect bilirubin above the upper limit of normal (ULN) not due to liver disease, increased lactate dehydrogenase (above ULN) without alternative etiology, or increased absolute reticulocytosis (above ULN) or bone marrow erythropoiesis in the absence of bleeding AND at least one marker direct or indirect autoimmune mechanism (positive direct antiglobulin for immunoglobulin G \[IgG\] or C3d, cold agglutinins).
   * Immune thrombocytopenia is defined by platelets ≤100,000/µL and increased megakaryocytes on the bone marrow exam.
   * Constitutional symptoms, defined as one or more of the following disease-related symptoms or signs, documented in the patient's record prior to randomization:
   * unintentional weight loss \>10 percent within 6 months prior to screening.
   * significant fatigue (inability to work or perform usual activities).
   * fevers \>100.5°F or 38.0°C for 2 or more weeks prior to screening without evidence of infection.
   * night sweats for more than 1 month prior to screening without evidence of infection.
4. Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node \>1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended.

   Laboratory
5. Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening and randomization.
6. Adequate hepatic and renal function
7. Men and women ≥ 18 years of age.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Exclusion Criteria:

1. Any prior treatment of CLL or SLL
2. Evidence of central nervous system (CNS) involvement with primary disease of CLL/SLL
3. History of other malignancies, except:

   * Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura
5. Known or suspected history of Richter's transformation.
6. Concurrent administration of \>20mg/day of prednisone within 7 days of randomization unless indicated for prophylaxis or management of allergic reactions (eg, contrast)
7. Known hypersensitivity to one or more study drugs
8. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
9. Any uncontrolled active systemic infection or an infection requiring systemic treatment that was completed ≤ 7 days before randomization.
10. Known bleeding disorders or hemophilia.
11. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
12. Known history of human immunodeficiency virus (HIV) or active with hepatitis B virus (HBV) or hepatitis C virus (HCV).
13. Major surgery within 4 weeks of randomization.
14. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
15. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
16. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
17. Concomitant use of warfarin or other vitamin K antagonists.
18. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
19. Lactating or pregnant
20. Unwilling or unable to participate in all required study evaluations and procedures.
21. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
B: Inclusion:

* Adult subjects with previously treated recurrent CLL who have measurable lymphadenopathy
* Require therapy for CLL
* Have experienced CLL progression \< 24 months since the completion of the last prior therapy
* Currently not sufficiently fit to receive cytotoxic therapy because of chemotherapy-induced bone marrow damage or comorbidities.
C: Inclusion Criteria:

1. Patients with untreated CLL or small lymphocytic lymphoma (SLL) with indication to treatment according to NCI Working Group guidelines.Patients that have received single agent rituximab will be allowed to participate in this study.
2. Age 65 or older
3. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0-2.
4. Adequate renal function indicated by serum creatinine less or equal to 2 and adequate hepatic function indicated as total bilirubin less or equal to upper level of normal and as alanine aminotransferase (ALT) less or equal 2 upper limit of normal (ULN).
5. Able to understand and sign Informed Consent after the investigational nature, study design, risks and benefits have been explained.
6. Able to adhere to the study visit schedule and other protocol requirements.
7. Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation can be enrolled in the study as long as they have a reasonable expectation to have been cured with treatment modality received.
8. Females of childbearing potential (FCBP). A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence
9. Continued from above. from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
10. Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy.
11. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
12. All patients must be able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to Acetylsalicylic Acid (ASA) may use warfarin or low molecular weight heparin.

Exclusion Criteria:

1. Known sensitivity to thalidomide or its derivatives.
2. Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood).
3. Known positivity for HIV or active hepatitis (B or C).
4. A serious medical condition, laboratory abnormality or psychiatric illness that would interfere with the ability of the patient to participate in this program according to the judgement of the Principal Investigator.
5. Active cardiovascular disease as defined by the New York Heart Association Class 3 or 4.
6. History of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
7. Concurrent use of other chemotherapy agents.
8. Pregnant or breast feeding females. Lactating females must agree not to breast feed while taking lenalidomide.
9. No known history of tuberculosis or recent exposure to tuberculosis.
D: Inclusion Criteria:

* Histologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
* No prior cytotoxic chemotherapy for their disease; prior therapy with single-agent rituximab is permitted
* Understand and voluntarily sign an informed consent document
* In cases of SLL, subjects must have at least one bidimensionally measurable lesion at least \>= 1.5 cm measured in one dimension
* Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 at study entry
* Absolute neutrophil count \>= 1500/uL
* Platelet count \>= 100,000/uL
* Subjects with neutrophils \< 1500/uL or platelets \< 100,000/uL with splenomegaly or extensive bone marrow involvement as the etiology for their cytopenias are eligible
* Subjects must have adequate renal function with a creatinine clearance of \>= 40 mL/min as determined by the Cockcroft-Gault calculation
* Total bilirubin =\< 2 x upper limit laboratory normal (ULN); subjects with non-clinically significant elevations of bilirubin due to Gilbert's disease are not required to meet these criteria
* Serum transaminases aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x ULN
* Serum alkaline phosphatase =\< 5 x ULN
* Disease-free of prior malignancies for \>= 2 years with the exception of basal or squamous cell skin carcinoma, carcinoma "in situ" of the breast or cervix, or localized prostate cancer (treated definitively with hormone therapy, radiotherapy, or surgery)
* Life expectancy of at least 3 months
* All study participants must be willing to be registered into the mandatory Revlimid REMS program after completion of induction chemoimmunotherapy and prior to maintenance therapy, and be willing and able to comply with the requirements of the Revlimid REMS program
* Subjects must not have a known history of hypersensitivity to mannitol
* Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory disease
* Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program
* Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects intolerant to aspirin may use warfarin or low molecular weight heparin) if clinically indicated
* Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be filled within 7 days as required by the Revlimid REMS® program) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy

Exclusion Criteria:

* Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document or complying with the protocol treatment
* Pregnant or breast-feeding females; lactating females must agree not to breast-feed while taking lenalidomide
* Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
* Subjects are not eligible if there is a prior history or current evidence of central nervous system or leptomeningeal involvement
* Known hypersensitivity to thalidomide
* Concurrent use of other anti-cancer agents or treatments
* Known to be positive for human immunodeficiency virus (HIV) or infectious hepatitis (type B or C)
* Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, or other cancer from which the subject has been disease free for at least 2 years
* Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously exposed to rituximab or other monoclonal antibody therapy
* Chronic hepatitis B or hepatitis C infection
* New York Heart Association class 3-4 heart failure
* More than one grade 2 or higher transaminase elevation

Answer: A