Loncastuximab Tesirine as a Maintenance Therapy after Autologous Stem Cell Transplant for the Treatment of High Risk Diffuse Large B-cell Lymphoma

Inclusion Criteria

• Signed informed consent form (ICF)
• Age >= 18 years
• Patients with relapsed refractory DLBCL with any of the following high-risk features for progression following autoSCT will be enrolled: * Primary refractory lymphoma (failure to achieve complete remission as determined by the treating physician) following 1st line anthracycline containing chemotherapy * Early relapsed lymphoma with an initial remission duration of less than 12 months following 1st line anthracycline containing chemotherapy * Failure to achieve complete remission following salvage chemotherapy and positive positron emission tomography (PET)-computed tomography (CT) as defined by Lugano criteria (Deauville score of 4 or 5) prior to autoSCT * Double hit lymphoma (DHL) or triple hit lymphoma (THL) confirmed by FISH testing by local pathology (defined as high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements) * Double expressor lymphoma (DEL) as confirmed by immunohistochemistry (IHC) by local pathology (MYC and BCL2 or BCL6 positivity) * CMYC rearranged (by fluorescence in situ hybridization [FISH]) DLBCL * High international protein index (IPI) score (>= 3 points) * Stage 3-4 disease at diagnosis * Extra-lymphatic disease * High grade B cell lymphoma
• Eligible to undergo autologous stem cell transplantation as per local investigator assessment
• Availability of biopsy specimens confirming DLBCL relapse. Archival formalin-fixed paraffin-embedded (FFPE) tissue blocks or 15 unstained slides serial sections (5-10 um in thickness) must be available prior to study enrollment. The pathology report must be available. IHC testing of CMYC, BCL2, and BCL6 expression, and FISH testing of CMYC, BCL2 and BCL6 gene rearrangement must be available prior to enrollment. CD19 expression status must be available prior to enrollment. Patients previously treated with CD19-targeted therapy (including chimeric antigen receptor [CAR] T) must have a subsequent biopsy and/or flow cytometry confirming CD19 positivity
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of at least 6 months
• Ability and willingness to comply with the study protocol procedures
• Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9 months after the last dose of loncastuximab tesirine. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 6 months after the patient receives his last dose of loncastuximab tesirine

Exclusion Criteria

• Contraindication to any of the individual components of autoSCT or loncastuximab tesirine
• Prior exposure to loncastuximab tesirine
• Clinically significant effusion i.e., ascites, pleural or pericardial effusion either requiring drainage or associated with shortness of breath
• Patients with ongoing toxicities of grade > 1 from previous treatments except alopecia
• Patients with clinically significant history of liver disease including cirrhosis or hepatitis (viral hepatitis). However, treated viral hepatitis can be allowed
• Patients with history of severe skin disorders including Steven-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
• Patients who are receiving any other investigational agents
• Grade 3b follicular lymphoma
• Burkitt’s lymphoma
• Patients with known brain, spinal, or cerebrospinal fluid (CSF) involvement
• Systemic steroids (prednisone > 20 mg/day or equivalent) and/or immunosuppressive medications
• Unstable cardiovascular function that could affect compliance with the protocol: * Symptomatic ischemia, or * Congestive heart failure (CHF) of New York Heart Association (NYHA) Class >= 3, or * Myocardial infarction (MI) within 3 months * Left ventricular ejection fraction < 45% based on echocardiogram or multigated acquisition (MUGA) scan obtained within 6 months prior to enrollment * History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator’s opinion, including complete left bundle branch block, second- or third-degree heart block
• Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg]) * Patients with occult or prior HBV infection (defined as negative HBsAg and positive hepatitis B core antibody [HBcAb]) may be included if HBV DNA polymerase chain reaction (PCR) is undetectable, provided that they are willing to undergo DNA testing on day 1 of every cycle of study treatment. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination or prior but cured hepatitis B are eligible
• Known history of human immunodeficiency virus (HIV) seropositive status
• Patients with a history of progressive multifocal leukoencephalopathy
• Creatinine > 1.5 x upper limit of normal (ULN) or a measured creatinine clearance < 40 mL/min (unless abnormal laboratory values are due to underlying lymphoma per the investigator)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN) (unless abnormal laboratory values are due to underlying lymphoma per the investigator)
• Total bilirubin >= 1.5 x ULN (unless abnormal laboratory values are due to underlying lymphoma per the investigator) * Patients with documented Gilbert disease may be enrolled if total bilirubin is =< 3 x ULN
• International normalized ratio (INR) or prothrombin time (PT) > 1.5 x ULN in the absence of therapeutic anticoagulation (unless abnormal laboratory values are due to underlying lymphoma per the investigator)
• Partial thromboplastin time (PTT) or activated (a)PTT >= 1.5 x ULN in the absence of a lupus anticoagulant (unless abnormal laboratory values are due to underlying lymphoma per the investigator)