Comparing 5 approaches for b-cell non-hodgkin lymphoma

Exclusion

• −Known or suspected hypersensitivity to any of the excipients of formulated study drug
• −Non-infectious hepatitis
• −Known HIV infection or AIDS
• −Active hepatitis B virus or hepatitis C virus infection
• −Patients documented to be CD19-negative
• −Part 2: History of another malignancy within 2 years, with the exception of:
• −Treated, non-melanoma skin cancers
• −Treated carcinoma in situ (e.g., breast, cervix)
• −Controlled, superficial carcinoma of the urinary bladder
• −T1a or b prostate carcinoma treated according to standard of careStandard of careThe treatment normally given for a condition outside a study.Read more →, with PSA within normal limits
• −Papillary thyroid carcinoma Stage I treated surgically for cure
• −Any of the following hematologic abnormalities at baselineBaselineYour starting measurements, taken before treatment begins.Read more → (transfusion allowed \> 5 days previous):
• −Hemoglobin \< 8.0 g/dL
• −Absolute neutrophil count \< 1,000 per mm3
• −Platelet count \< 75,000 per mm3
• −Any of the following laboratory abnormalities at baseline:
• −Total bilirubin \> 1.5 × upper limit of normal (ULN); \> 3 × ULN if with Gilbert's Syndrome
• −AST or ALT \> 3 × ULN; \> 5 × ULN if due to hepatic involvement by tumor
• −Estimated GFR ≤ 60 mL/min corrected for BSA
• −Albuminuria defined as urine albumin to creatinine ratio \< 30 mg/g or \< 3 mg/mmol) by spot urine albumin
• −Any of the following coagulation parameter abnormalities at baseline unless on a stable dose of anticoagulant therapy for a prior thrombotic event:
• −PT or INR \> 1.5 × ULN; \> 3× ULN if anticoagulated)
• −PTT \> 1.5 × ULN; \> 3× ULN if anticoagulated
• −Any of the following laboratory abnormalities at baseline aimed at assessing renal function:
• −Estimated glomerular filtration rate (eGFR) ≤ 60 mL/min, corrected for BSA.
• −Albuminuria defined as urine albumin to creatinine ratio (UACR) ≥ 45 mg/g or ≥ 4.5 mg/mmol by spot urine albumin
• −Patients with:
• −Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks unless adequately treated and stable
• −Active uncontrolled bleeding or a known bleeding diathesis
• −Significant cardiovascular disease or condition, including:
• −Congestive heart failure or angina pectoris requiring therapy
• −Ventricular arrhythmia requiring therapy or other uncontrolled arrhythmia
• −Severe conduction disturbance (e.g., 3rd degree heart block)
• −QTc interval ≥ 480 milliseconds
• −Left ventricular ejection fraction below the lower limit of normal or \< 50% by MUGA scan or echocardiogram
• −Class III or IV cardiovascular disease according to the New York Heart Association Functional Classification
• −History of acute coronary syndromes (e.g., MI, unstable angina), coronary angioplasty, stenting, or bypass within 6 months
• −Significant liver disease, including:
• −Hepatic cirrhosis (Child-Pugh Class B and Class C)
• −Significant pulmonary disease or condition, including:
• −Significant symptomatic COPD, as assessed by the InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →
• −History or any current evidence on imaging studies of interstitial lung disease, pulmonary fibrosis
• −History of pulmonary inflammatory disease, pneumonitis, ARDS
• −History of pneumonia within 1 month
• −Significant corneal disease or condition, including history of or current evidence of keratitis
• −Clinically significant CNS disease or condition including PML, epilepsy, vasculitis, or neurodegenerative disease. Also including TIA or stroke within 6 months
• −Any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever \> 38ºC within 2 weeks
• −Autoimmune disease or condition requiring systemic steroids or other immunosuppressive medications
• −Unresolved Grade \> 1 AEAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → associated with any prior antineoplastic therapy (except persistent Grade 2 alopecia, peripheral neuropathy, decreased hemoglobin, neutropenia, lymphopenia, hypomagnesemia, and/or endocrine end-organ failure being adequately managed by HRT)
• −Inadequate recovery from a surgical procedure, or a major surgical procedure within 4 weeks
• −Any other serious, life-threatening, or unstable preexisting medical condition, including significant organ system dysfunction, or clinically significant laboratory abnormality(ies)
• −A psychiatric disorder or altered mental status that would preclude understanding of the informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → process
• −Drugs and Other Treatments to be Excluded:
• −Receipt of:
• −Any tumor vaccine within 6 weeks (must have progressed if previously received)
• −Prior autologous/allogeneic CAR-T therapy if known to be CD19-negative after
• −Any other antineoplastic agent for the primary malignancy without delayed toxicity within 3 weeks or 5 plasma half-lives, whichever is shortest (except nitrosoureas and mitomycin C within 6 weeks)
• −Any other investigational treatments within 3 weeks
• −Drugs known to impair renal function, including:
• −NSAIDS within 3 days
• −Aminoglycoside antibiotics, amphotericin B, etc. within 1 week
• −Bisphosphonates within 1 month
• −Prior solid organ transplant
• −Allogeneic HSCT within 6 months, or:
• −If receiving immunosuppression
• −If with active evidence of GVHD
• −Autologous hematopoietic stem cell transplantation (HSCT) within 3 months
• −Radiotherapy:
• −To target lesions within 4 weeks unless progression of the lesion has been documented
• −To non-target lesions within 1 week
• −Live/live-attenuated vaccines against infectious diseases within 4 weeks
• −Immunosuppressive or systemic glucocorticoid therapy (\> 10 mg prednisone daily or equivalent) within 2 weeks
• −Prophylactic use of hematopoietic growth factors within 1 week
• −Herbal therapies and supplements within 2 weeks
• −Strong inhibitors of cytochrome P450 within 2 weeks
• −Women who are pregnant or intending to become pregnant before, during, or within 8 months after the last dose of study drug; women who are breastfeeding
• −Central nervous system (CNS) lymphoma, leptomeningeal infiltration, or spinal cord compression not controlled by prior surgery or radiotherapy; symptoms suggesting CNS involvement
• −Any CD19-targeted therapy within 4 weeks