• Age \>= 18 years willing to provide consent and follow-up

• Diagnosis of CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria (Hallek et al., 2018) or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) 2008 criteria (Harris, 1999). This includes previous documentation of:

‣ Biopsy-proven SLL according to WHO 2008 criteria, or

⁃ Diagnosis of CLL according to IWCLL 2018 criteria as evidenced by all of the following:

• Peripheral blood B cell count of \>= 5 x 10\^9/L consisting of small to moderate size lymphocytes (If there are enough evidence to document the prior diagnosis of CLL, it is not required to meet the criteria of peripheral blood B cell count more than 5 x 10\^9/L )

∙ Immunophenotyping consistent with CLL defined as:

‣ The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 \[typically dim expression\], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)

⁃ Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. immunoglobulin heavy chain variable \[IGHV\] analysis)

∙ NOTE: Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL

∙ Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy

∙ If prior CLL diagnosis was confirmed, or CLL diagnosis was confirmed on bone marrow examination or tissue biopsy, peripheral blood B cell count less than 5 x 10\^9/L is allowed

• Biopsy proven Richter's transformation of the CLL

‣ NOTE: Previously treated patients including CLL therapy can be enrolled. If Richter's transformation (RT) developed from prior untreated CLL and has not received any RT directed therapy, then patient is not eligible

• Richter patients with prior or concurrent CLL diagnosis and do not have other option for standard therapy per treating physician's discretion

• Measurable disease can be detected in positron emission tomography (PET) or computed tomography (CT) (\>= 1 cm in diameter)

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

• Absolute neutrophil count \>= 0.7 x 10\^9/L unless marrow was involved by CLL or RT, then absolute neutrophil count (ANC) \>= 0.3 x 10\^9/L (=\< 14 days prior to registration)

• Platelet count \>= 40 x 10\^9/L unless marrow was involved by CLL or RT, then platelet \>= 30 x 10\^9/L without transfusion =\< 1 week prior to study registration (=\< 14 days prior to registration)

• Hemoglobin (Hgb) \>= 8 unless marrow was involved by CLL or RT, then Hgb \>= 7 without transfusion =\< 1 week prior to study registration (=\< 14 days prior to registration)

• Total bilirubin =\< 1.5 x upper limit of normal (ULN) unless due to confirmed Gilbert's disease (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician (=\< 14 days prior to registration)

‣ Note: If total bilirubin is \> 1.5 x ULN, a direct bilirubin should be performed and must be =\< upper limit of normal

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X ULN unless liver metastases are present, in which case it must be =\< 5 x ULN (=\< 14 days prior to registration)

• Calculated creatinine clearance of \> 30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) (=\< 14 days prior to registration)

• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only

‣ NOTE: The following restrictions apply while the patient is receiving study treatment and for the specified times before and after:

• Female patient of child-bearing potential

‣ Female patients of childbearing potential who are not abstinent and intend to be sexually active with a non sterilized male partner must use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (180 days after the last dose of study treatment). Non-sterilized male partners of a female patient of childbearing potential must use male condom plus spermicide throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Female patients should also refrain from breastfeeding throughout this period

∙ Male patients with a female partner of childbearing potential

‣ Non-sterilized male patients who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide from the time of screening throughout the total duration of the drug treatment and the drug washout period (180 days after the last dose of study treatment). However, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Male patients should refrain from sperm donation throughout this period

∙ Female partners (of childbearing potential) of male patients must also use a highly effective method of contraception throughout this period

∙ Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal

∙ Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

‣ Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution

⁃ Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago

∙ Highly effective methods of contraception, defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly are described below. Note that some contraception methods are not considered highly effective (e.g. male or female condom with or without spermicide; female cap, diaphragm, or sponge with or without spermicide; non-copper containing intrauterine device; progestogen-only oral hormonal contraceptive pills where inhibition of ovulation is not the primary mode of action \[excluding Cerazette/desogestrel which is considered highly effective\]; and triphasic combined oral contraceptive pills)

∙ Effective methods include:

‣ Copper T intrauterine device

⁃ Levonorgestrel-releasing intrauterine system (e.g., Mirena)

⁃ Implants: Etonogestrel-releasing implants: e.g. Implanon or Norplant

⁃ Intravaginal: Ethinylestradiol/etonogestrel-releasing intravaginal devices: e.g. NuvaRing

⁃ Injection: Medroxyprogesterone injection: e.g. Depo-Provera

⁃ Combined pill: Normal and low dose combined oral contraceptive pill

⁃ Patch: Norelgestromin/ethinylestradiol-releasing transdermal system: e.g. Ortho Evra

⁃ Minipill: Progesterone based oral contraceptive pill using desogestrel: Cerazette is currently the only highly effective progesterone-based

⁃ Tubal ligation

• Provide informed written consent

• Willing to return to enrolling institution for follow-up

• Willing to provide tissue, blood, and bone marrow samples for mandatory correlative research purposes