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\. Documented informed consent of the participant and/or legally authorized representative |
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\. Agreement to allow the use of archival tissue from diagnostic tumor biopsies If unavailable, exceptions may be granted with Study PI approval |
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\. Age: ≥ 18 years |
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\. ECOG ≤ 2 |
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\. Histologically confirmed Mantle Cell Lymphoma (MCL) |
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Evidence of positive BAFF-R expression on the MCL cells at the time of enrollment is required. Archival tissue is allowed if there is a significant safety risk for a repeat biopsy or if the lymphoma site is not accessible |
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Subjects with other relapsed or refractory BAFFR+ B cell lymphoma with no standard of care options are allowed during initial dose escalation phase, not the dose expansion phase |
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\. Relapsed/refractory disease after failure of at least 1 prior regimen |
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Participants who have primary refractory MCL (with or without prior BTK inhibitor) defined as lymphoma did not respond to a first line therapy or the response did not last longer than 6 months from an initial response, or |
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Participants who have relapsed MCL defined as recurrence of disease after an initial response lasting longer than 6 months, must have had at least 1 prior regimen that must include a BTK inhibitor, or |
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Participants with newly diagnosed MCL without standard of care (SOC) options (e.g., TP53 mutation, ineligible for intensive chemotherapy) are eligible after discussion with PI |
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\. Measurable disease by CT scan (≥1.5 cm) or evidence of blood, gastrointestinal |
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skin, bone marrow or spleen involvement |
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\. Prior CAR T cell therapy is allowed if at least 90 days prior to leukapheresis procedure |
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\. Fully recovered from the acute toxic effects (except alopecia) to ≤ Grade 1 to prior anti-cancer therapy |
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\. No known contraindications to leukapheresis, steroids or tocilizumab |
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\. Total bilirubin ≤ 1.5 X ULN (unless has Gilbert's disease), then ≥ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN) |
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\. AST < 3 x ULN |
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\. ALT < 3 x ULN |
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\. Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula |
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\. Left ventricular ejection fraction (LVEF) ≥ 45% Note: To be performed within 28 days prior to start of protocol therapy |
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\. QTc ≤ 480 ms Note: To be performed within 28 days prior to start of protocol therapy |
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\. O2 saturation > 91% on room air |
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\. Seronegative for HIV Ag/Ab combo, HCV, active HBV (Surface Antigen Negative) |
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If seropositive for HIV, HCV or HBV (surface antigen or core antibody positive), nucleic acid quantitation must be performed. Viral load must be undetectable |
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\. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test |
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If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test |
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will be required |
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__20. Agreement by females and males of childbearing potential to use an effective method |
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of birth control or abstain from heterosexual activity for the course of the study through |
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at least 3 months after the last dose of protocol therapy |
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Childbearing potential defined as not being surgically sterilized (men and women) or have |
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not been free from menses for > 1 year (women only) |
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Prior allogeneic stem cell transplant
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Autologous stem cell transplant within 90 days at the time of enrollment
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Concurrent use of systemic steroids or chronic use of immunosuppressant
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medications. Recent or current use of inhaled steroids is not exclusionary
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Physiologic replacement of steroids (i.e., prednisone ≤ 7.5 mg/day or hydrocortisone ≤
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mg/day) is allowed. During study participation, participants may receive systemic
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corticosteroids as needed for treatment-emergent comorbid conditions
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Cardiac lymphoma involvement
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Requirement for urgent therapy due to tumor mass effects such as bowel obstruction
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or blood vessel compression
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Auto-immune disease or condition requiring systemic immunosuppressant therapy
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including uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic
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thrombocytopenic purpura (ITP)
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Primary immunodeficiency
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Class III/IV cardiovascular disability according to the New York Heart Association
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(NYHA) Classification
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History of clinically significant arrhythmia. Paroxysmal atrial fibrillation or
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flutter that is stable on medical management at least 2 weeks prior to enrollment is
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allowed
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History or prior diagnosis of optic neuritis or other immunologic or inflammatory
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disease affecting the central nervous system, including seizure disorder
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History of allergic reactions attributed to compounds of similar chemical or
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biologic composition to study agent, including lymphodepletion agents and tocilizumab
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History of stroke or intracranial hemorrhage within 6 months of enrollment
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History of venous thrombotic embolism (VTE) within 6 months of enrollment with
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exception of central line associated VTE
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History of other malignancies, except for malignancy surgically resected (or
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treated with other modalities) with curative intent, basal cell carcinoma of the skin
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or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer
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malignancy treated with curative intent with no known active disease present for ≥ 3
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years
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Clinically significant uncontrolled illness
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Active systemic uncontrolled infection requiring antimicrobials
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Active CNS MCL or History of CNS MCL within 3 months prior to screening
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Females only: Pregnant or breastfeeding i. Any other condition that would, in the
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Investigator's judgment, contraindicate the patient's participation in the clinical
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study due to safety concerns with clinical study procedures
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Prospective participants who, in the opinion of the investigator, may not be able
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to comply with all study procedures (including compliance issues related to
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feasibility/logistics)
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