Phase II Study of Pirtobrutinib With Venetoclax In Relapsed-Refractory MCL (Mantle Cell Lymphoma) Patients

Inclusion Criteria: 1. Confirmed diagnosis of mantle cell lymphoma in tissue biopsy by hematopathology with/without chromosome translocation t(11;14), (q13;q32) and/or overexpress cyclin D1 in tissue biopsy. Cyclin D1 negative MCL (confirmed by hematopathology at MDACC are allowed). 2. The patient is able to take oral medications 3. Relapsed MCL (irrespective of prognostic factors) including any lines or prior therapy or patients who had prior ibrutinib, acalabrutinib, zanubrutinib, other BTK inhibitor or anti CD19-CART therapy, single agent or in combination (without prior venetoclax) or relapsed high risk MCL including any or all of the following (Blastoid/pleomorphic histology), High Ki-67 (≥50%), TP53 mutated or del17p by FISH, NSD2, NOTCH2, CDKN2A mutated or MYC positive by FISH or MYC, Bcl2 amplification, complex karyotype or high risk biologic MIPI score 4. Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. 5. Age from \>=18 years at the time of signing the informed consent. 6. Patients may have at least 1 site of radiographically assessable disease (i.e., lymph node longest diameter \[LDi\] \>= 1.5 cm, not necessary for disease assessable by positron emission tomography \[PET\]/computerized tomography \[CT\], extra nodal site \>= 1.0 cm in LDi. Patients with BM only or GI only relapse are allowed. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. 8. Disease free of prior malignancies with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy \> 3 years pertaining to prior malignancy. PI could use judgment in the best interest of patients. 9. Patients must have relapsed or refractory MCL (irrespective of prior BTK inhibitor or anti CD19 CART exposure). 10. Prothrombin time (or international normalized ratio) and partial thromboplastin time not to exceed 1.2 times the institutional upper limit of normal range (patients with an elevated prothrombin time and known lupus anticoagulant may be eligible for participation after consulting the IND sponsor). 11. Adequate BM function independent of growth factor or PRBC or platelet transfusion support (within 14 days of Screening assessment and criteria must be met on C1D1 without transfusion/G-CSF within 7 days of assessment, per local laboratory reference range at screening as follows: 1. platelet count \>=50, 000/mm3; 2. absolute neutrophil count (ANC) \>= 1000/mm3 unless cytopenia is clearly due to marrow involvement from MCL 3. total hemoglobin \>= 8 g/dL (without transfusion support within 2 weeks of screening); If any of the above-mentioned cytopenias (a-c) are present due to significant BM involvement, at least 30% BM involvement by MCL (requiring transfusion or granulocyte colony-stimulating factor \[G-CSF\] support) MCL patients may proceed with enrollment after discussion with the PI or Co-PI. Cytopenias may not be due to evidence of myelodysplastic syndrome (MDS) or hypoplastic BM. 12. Adequate organ function as defined by the following laboratory values: 1. Creatinine clearance. \>=30 mL/min (by Cockcroft-Gault method, APPENDIX I), 2. Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN with documented liver involvement and/or Gilbert's Disease or controlled immune hemolysis or considered an effect of regular blood transfusions. 3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3 x ULN, or \< 5 x upper limit of normal if hepatic metastases are present. 13. Projected life expectancy of \>12 weeks pertaining to lymphoma. 14. Female patients must be surgically sterile, postmenopausal (for at least 1 year), or have confirmed negative results for a pregnancy test at screening, on a blood or urine sample obtained within 7 days prior to initiation of study treatment. 15. Women of childbearing potential and men with female partners of childbearing potential must be willing to use an effective form of contraception for at least 6 months after the last dose of study treatment. Patient enrolled into the Pirtobrutinib+ venetoclax study should use an effective form of contraception for 6 months after the last dose of Pirtobrutinib in combination with venetoclax, whichever time period is longer. Recommended methods of highly effective birth control are: * Hormonal contraception (birth control pills, patches, or rings) * Intrauterine device (IUD) * Birth control injections * Double barrier methods (diaphragm with spermicidal gel or condoms with birth control foam) * Sterilization of participant or partner ("tubes tied" or vasectomy) Willingness of men and women of reproductive potential (defined as following menarche and not postmenopausal \[and 2 years of non-therapy-induced amenorrhea\] or surgically sterile) to observe conventional and highly effective birth control methods with failure rates of \< 1% for the duration of treatment and for 6 months following the last dose of study treatment; this must include barrier methods such as condom or diaphragm with spermicidal gel. Women of reproductive potential are defined as following menarche and not postmenopausal (and 2 years of non-therapy-induced amenorrhea) or surgically sterile. For male subjects with a non-pregnant female partner of child-bearing potential and a woman of child-bearing potential one of the following highly effective birth control methods with a failure rate of less than 1% per year when used consistently and correctly are recommended: Combined estrogen and progestin containing hormonal contraception associated with inhibition of ovulation given orally, intravaginally, or trans dermally, progestin-only hormo