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).
• +66 more criteria