Using acalabrutinib to prevent relapse in patients with large B-cell lymphoma

Inclusion Criteria:

* Ages 18-70 years
* One of the following:

  * Patients undergoing autologous stem cell transplantation (ASCT) or any Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T-cell therapy product for:

    * High grade B-cell lymphoma (double or triple hit) with rearrangements in bcl-2 and/or bcl-6, and rearrangement in myc
    * Large B-cell lymphoma with a history of secondary CNS involvement
    * Histologic transformation of indolent lymphoma to large B-cell lymphoma, including marginal zone lymphoma, follicular lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), lymphoplasmacytic leukemia, or Waldenstrom macroglobulinemia
    * High risk international prognostic index (IPI) score 4 or 5, at diagnosis or prior to CAR T-cell leukapheresis
  * Patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for large B-cell lymphoma
* Eastern Cooperative Oncology Group (ECOG) 0-2
* Requirements for post-ASCT and post-alloHCT participants:

  * Disease status of partial response (PR) or complete response (CR) prior to transplantation
  * Receive reduced-intensity conditioning regimen
  * Enrollment no later than day +90
* Requirements for post-CAR T-cell therapy participants:

  * Disease status of PR or CR after post-CAR T-cell therapy positron emission tomography (PET)-computed tomography (CT) at 1-3 months
  * Enrollment no later than day +104
* Ability to give full informed consent
* Female subjects who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib
* Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty
* Absolute neutrophil count (ANC) \> 500/uL (microliters)
* Platelets \> 50,000/uL independent of transfusions
* Hemoglobin \> 8 g/dL independent of transfusions
* Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN)
* Total bilirubin =\< 1.5 x ULN, unless directly attributable to Gilbert's syndrome
* Creatinine clearance \>= 60 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR) and serum creatinine (Cr) =\< 1.8 mg/dL

Exclusion Criteria:

* Cord blood as donor source in alloHCT
* New York Heart Association Class III or IV
* Left ventricular ejection fraction \< 50%
* Estimated glomerular filtration rate \< 30 mL/min
* Concurrent long-term use of posaconazole or other strong CYP3A4 inhibitors and unable to replace with equivalent medication
* Acute or chronic graft-versus-host disease (GvHD) \>= stage 3 at time of enrollment
* Received packed red blood cells (pRBC) transfusion within the past 2 weeks
* Received platelet transfusion within the past 1 week
* Active invasive fungal infection
* Active bacterial or viral infection until resolution of the infection
* History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
* Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug
* Major surgical procedure within 30 days before the first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
* Refractory nausea and vomiting, inability to swallow the formulated product, or malabsorption syndrome; chronic gastrointestinal disease, gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment
* Received a live virus vaccination within 28 days of first dose of study drug
* Known history of infection with human immunodeficiency virus (HIV)
* History of bleeding diathesis (e.g., hemophilia, von Willebrand disease)
* Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
* Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor or inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited
* Breastfeeding or pregnant
* Concurrent participation in another therapeutic clinical trial