Tafasitamab and Rituximab for Front-Line Treatment of Post-Transplant Lymphoproliferative Disorder

Inclusion Criteria:

• Written informed consent obtained to participate in the study and Health InsurancePortability and Accountability Act (HIPAA) authorization for release of personalhealth information

• Age >= 18 years at the time of consent

• Karnofsky scale > 30% or Eastern Cooperative Oncology Group (ECOG) =< 3 (can beassessed after pre-phase steroids)

• Histological evidence of B-cell PTLD (monomorphic and polymorphic) following solidorgan transplantation; expresses CD19 and CD20, with or without EBV association,confirmed after biopsy or resection of tumor

• Measurable disease of > 1.5 cm in diameter and/or bone marrow involvement

• Subjects having undergone heart, lung, liver, kidney, pancreas, small intestinetransplantation or a combination of the organ transplantations mentioned

• No prior lines of therapy for PTLD (palliative radiation, steroids, antiviraltherapy, and reduction in immunosuppression are allowed)

• Human immunodeficiency virus (HIV) infection is allowed if viral load isundetectable at time of enrollment and CD4+ count > 200 cells/uL

• Expected survival greater than 30 days

• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L (obtained within 14 days prior toinitiating study treatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meetcriteria for study entry are allowed. Furthermore, changes in laboratoryparameters during the study should not be considered adverse events unless theymeet criteria for dose modification(s) of study medication outlined by theprotocol and/or worsen from baseline during therapy

• Platelets >= 50 x 10^9/L (obtained within 14 days prior to initiating studytreatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meetcriteria for study entry are allowed. Furthermore, changes in laboratoryparameters during the study should not be considered adverse events unless theymeet criteria for dose modification(s) of study medication outlined by theprotocol and/or worsen from baseline during therapy

• Creatinine clearance (mL/min) >= 30 mL/min (obtained within 14 days prior toinitiating study treatment)

• Cockcroft-Gault Equation

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meetcriteria for study entry are allowed. Furthermore, changes in laboratoryparameters during the study should not be considered adverse events unless theymeet criteria for dose modification(s) of study medication outlined by theprotocol and/or worsen from baseline during therapy

• Bilirubin =< 3.0 x upper limit of normal (ULN). Subjects with Gilbert's syndrome maybe enrolled despite a total bilirubin level > 3.0 mg/dL if their conjugatedbilirubin is =< 3.0 x ULN) (obtained within 14 days prior to initiating studytreatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meetcriteria for study entry are allowed. Furthermore, changes in laboratoryparameters during the study should not be considered adverse events unless theymeet criteria for dose modification(s) of study medication outlined by theprotocol and/or worsen from baseline during therapy

• Aspartate aminotransferase (AST) =< 3.0 x ULN (obtained within 14 days prior toinitiating study treatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meetcriteria for study entry are allowed. Furthermore, changes in laboratoryparameters during the study should not be considered adverse events unless theymeet criteria for dose modification(s) of study medication outlined by theprotocol and/or worsen from baseline during therapy

• Alanine aminotransferase (ALT) =< 3.0 x ULN (obtained within 14 days prior toinitiating study treatment)

• Note: Hematology and other lab parameters that are =< grade 2 BUT still meetcriteria for study entry are allowed. Furthermore, changes in laboratoryparameters during the study should not be considered adverse events unless theymeet criteria for dose modification(s) of study medication outlined by theprotocol and/or worsen from baseline during therapy

• Females of childbearing potential must have a negative serum pregnancy test within 3days prior to registration. NOTE: Females are considered of childbearing potentialunless they are surgically sterile (have undergone a hysterectomy, bilateral tuballigation, or bilateral oophorectomy) or they are naturally postmenopausal for atleast 12 consecutive months. Documentation of postmenopausal status must be provided

• Females of childbearing potential must be willing to abstain from heterosexualactivity or to use 2 forms of effective methods of contraception from the time ofinformed consent until 12 months after treatment the last dose of rituximab ortafasitamab. The two contraception methods can be comprised of two barrier methods,or a barrier method plus a hormonal method or an intrauterine device that meets < 1%failure rate for protection from pregnancy in the product label

• Male subjects with female partners must have had a prior vasectomy or agree to usean adequate method of contraception (i.e., double barrier method: condom plusspermicidal agent) starting with the first dose of study therapy through 12 monthsafter the last dose of rituximab

• Subjects with prior or concurrent malignancy whose natural history or treatment doesnot have the potential to interfere with the safety or efficacy assessment of theexperimental regimen are eligible for the trial

• Subject is willing and able to comply with study procedures based on the judgementof the investigator or protocol designee

Exclusion Criteria:

• Uncontrolled active infection. Patients requiring systemic therapy are eligible ifthe infection is deemed controlled by the investigator

• Post-transplant lymphoproliferative disorder following liquid transplantation

• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use whilethe mother is being treated on study and lactating females must agree to notbreastfeed while taking study drugs)

• Subjects with central nervous system (CNS) involvement by PTLD

• Uncontrolled concomitant illness including, but not limited to, symptomaticcongestive heart failure (New York Heart Association [NYHA] class III or IV),unstable angina pectoris, myocardial infarction within 1 month prior to enrollment,uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe non-compensatedhypertension (systolic blood pressure >= 180 mmHg or diastolic blood pressure >= 120mmHg)

• History of progressive multifocal leukoencephalopathy

• Active hepatitis B infection with positive viral polymerase chain reaction (PCR)from the blood. Subjects with active hepatitis B infection and undetectable viralPCR from the blood will be allowed with concurrent use of entecavir suppression

• Prior treatment for PTLD with the exception of radiation, antivirals, steroids andreduced immunosuppression

• Electrocardiogram (ECG) abnormality at screening has to be documented by theinvestigator as not medically relevant

• Any condition, including the presence of laboratory values which is deemed by theclinician to place the subject at an unacceptable risk or confounds the ability tointerpret the data from this study

• Live virus vaccines must not be administered within 28 days of the start of studytreatment

• Any investigational treatments must have been completed at least 7 days prior to thestart of study treatment