• Patients must have a diagnosis of CLL/CLL and have high-risk cytogenetic features or molecular features, defined as: del(17p), mutated TP53, complex metaphase karyotype (defined as 3 unrelated chromosomal abnormalities, present in at least 2 metaphases on conventional, stimulated cytogenetic analysis)

• \*\*\* Note: some patients treated with ibrutinib or acalabrutinib may no longer have detectable FISH, karyotypic or molecular abnormalities after 12 months of therapy. These patients will be eligible if they fulfill the above criteria on a bone marrow biopsy or peripheral blood specimen taken either prior to starting ibrutinib or acalabrutinib, provided they did not receive treatment for their CLL between the date of the lab test and starting ibrutinib or acalabrutinib or at some time during their ibrutinib therapy and analyzed at a CLIA-accredited laboratory.

• Patients must have received at least 12 months of ibrutinib or acalabrutinib therapy and have measurable CLL by at least one of the following:

‣ Absolute monoclonal lymphocyte count \> 4000/L; OR

⁃ Measurable lymph nodes with at least one node \>1.5 cm in diameter on CT; OR

⁃ Bone marrow with \>/= 30% lymphocytes on aspirate differential OR

⁃ Detectable CLL cells using a standardized flow cytometry assay for minimal residual disease

• Age 18 years or older.

• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.

• Patients must have adequate renal and hepatic function:

‣ Serum bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease.

⁃ Serum creatinine clearance of 50ml/min (calculated or measured).

⁃ ALT and AST ≤3.0 x ULN, unless clearly due to disease involvement.

• Adequate bone marrow function:

‣ Platelet count of greater than 50,000/µl, with no platelet transfusion in prior 2 weeks.

⁃ ANC ≥1000/µl in the absence of growth factor support unless due to compromised bone marrow production from CLL, indicated by 80% CLL in marrow.

⁃ Hemoglobin ≥8mg/dL.

• INR \<1.5.

• Adequate cardiac function, as assessed by:

‣ Absence of uncontrolled cardiac arrhythmia.

⁃ Echocardiogram demonstrating LVEF ≥35%.

⁃ NYHA functional class ≤2.

• Ability to provide informed consent and adhere to the required follow-up.

⁃ Women of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drugs and must agree to use use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence , or sterilized partner) and a barrier method (eg., condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days after the last dose of study drug. Women of non-childbearing potential are those who are postmenopausal (defined as absence of menses for ≥1 year) or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use effective contraception, defined above, during the study and for 30 days following the last dose of study drug.

⁃ Patients or their legally authorized representative must provide written informed consent.