• Documented informed consent of the participant and/or legally authorized representative

• Be willing to provide tissue from a fresh core or excisional biopsy (performed as standard of care) of a tumor lesion prior to starting study therapy or from diagnostic tumor biopsies

‣ If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Age: ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) ≤ 2

• Histologically confirmed diagnosis of mantle cell lymphoma according to the World Health Organization (WHO) classification with a characteristic immunophenotypic profile with CD5+, CD20+, and with either cyclin D1 expression by immunohistochemistry (IHC), or positive by fluorescence in situ hybridization (FISH) or cytogenetics for the t(11,14) translocation, or both. Patients whose tumor is negative for cyclin D1 expression are allowed providing hemato-pathology confirmation of the diagnosis of MCL

‣ Relapsed or refractory disease after at least 1 prior line of systemic therapy

⁃ Relapse must have been confirmed histologically with hematopathology review. Exceptions may be granted with study PI approval

• Patient must be receiving treatment with single agent ibrutinib or another covalent BTK inhibitor (e.g., acalabrutinib, zanubrutinib), and must have previously achieved complete response (CR) or partial response (PR) to the BTK inhibitor, and must show evidence of progressive MCL at the time of enrollment

• Radiographically measurable disease by Lugano criteria (e.g., one or more nodal sites of disease ≥ 1.5 cm and/or extranodal sites of disease ≥ 1.0 cm in longest dimension)

‣ If measurable bone marrow involvement or circulating disease has been confirmed in the absence of radiographically measurable disease, exceptions may be granted with study PI approval

• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy

• WITHOUT BONE MARROW INVOLVEMENT: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3

‣ NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement

• WITH BONE MARROW INVOLVEMENT: ANC ≥ 500/mm\^3

‣ NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement

• WITHOUT BONE MARROW INVOLVEMENT: Platelets ≥ 75,000/mm\^3

‣ NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement

• WITH BONE MARROW INVOLVEMENT: Platelets ≥ 25,000/mm\^3

‣ NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement

• Total bilirubin ≤ 4 x upper limit of normal (ULN) (If hepatic involvement by lymphoma, or Gilbert's disease: ≤ 3 x ULN)

• Aspartate aminotransferase (AST) ≤ 3 x ULN (If hepatic involvement by lymphoma: AST ≤ 5 x ULN)

• Alanine aminotransferase (ALT) ≤ 3 x ULN (If hepatic involvement by lymphoma: ALT ≤ 5 x ULN)

• Creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula

• IF NOT RECEIVING ANTICOAGULANTS: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN

• IF ON ANTICOAGULANT THERAPY: PT must be within therapeutic range of intended use of anticoagulants

• IF NOT RECEIVING ANTICOAGULANTS: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN

• Left ventricular ejection fraction (LVEF) ≥ 50%

• Mean corrected QT interval (QTc) (calculated from 3 electrocardiograms using Fridericia formula) ≤ 480 ms

• WOMEN OF CHILDBEARING POTENTIAL: (WOCBP): Negative urine or serum pregnancy test

‣ If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females and males of childbearing potential to abstain from heterosexual intercourse or use a highly effective method of birth control (defined as those resulting in a failure rate of \< 1% per year) during the treatment period until at least 90 days after the last dose of pacritinib and until at least 30 days after the last dose of BTK inhibitor

‣ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) with no identified cause other than menopause

⁃ Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormone releasing intrauterine devices, and copper intrauterine devices. Note that oral contraceptives or progestin injection (e.g., Depo-Provera) alone are not considered highly effective methods of contraception on their own in combination with pacritinib; an additional barrier method (diaphragm with spermicidal gel or condoms with spermicide), double-barrier methods (diaphragm with spermicidal gel and condoms with spermicide), partner vasectomy, or total abstinence are required