Tafasitamab in Combination with Lenalidomide and Rituximab for the Treatment of Follicular Lymphoma and Marginal Zone Lymphoma

Inclusion Criteria

• Diagnosis of either: * Histologically confirmed marginal zone lymphoma, OR * Histologically confirmed CD20+ follicular lymphoma stage 1, 2 or 3a
• No prior systemic therapy for lymphoma
• Must be in need of treatment as evidenced by one or more of the following criteria: * Bulky disease defined as: ** A nodal or extranodal (except spleen) mass > 7cm in its greater diameter or, ** Involvement of at least 3 nodal or extranodal sites (each with a diameter greater than > 3 cm) * Presence of at least one of the following B symptoms: ** Fever (> 38C) of unclear etiology ** Night sweats ** Weight loss greater than 10% within the prior 6 months * Any other symptoms attributable to lymphomatous mass * Endangerment of vital organ due to lymphomatous mass including but not limited to: ** Symptomatic or massive splenomegaly ** Compression syndrome (including but not limited to ureteral, orbital, gastrointestinal) * Pleural, pericardial or ascitic effusion regardless of cell count * Follicular lymphoma in leukemic phase (> 5 x 10^9/L circulating cells) OR: * Follicular lymphoma graded high-risk by Follicular Lymphoma International Prognostic Index- 2 (FLIPI2) score
• Follicular lymphoma must have measurable disease on PET scan per Lugano criteria; marginal zone lymphoma must have measurable disease on CT scan per Lugano criteria if disease is not PET-avid
• Age 18 years or older
• Performance status of Eastern Cooperative Oncology Group (ECOG) ≤ 1 unless due to lymphoma
• Hemoglobin ≥ 8.0 g/dL (within 14 days of study registration) without transfusion support unless due to lymphoma
• Absolute neutrophil count (ANC) ≥ 1,500/mcL (within 14 days of study registration) unless due to lymphomatous involvement of bone marrow or due to benign ethnic neutropenia in designated ethnicities (African decent)
• Platelets ≥ 75,000/mcL (within 14 days of study registration) (unless documented reduction due to lymphoma, then platelets ≥ 30,000/mcL)
• Calculated creatinine clearance (Cockcroft-Gault formula) ≥ 30 mL/min (within 14 days of study registration)
• Alanine aminotransferase (ALT) ≤ 3 times upper limit of institutional normal (within 14 days of study registration) (unless documented Gilbert’s syndrome or liver involvement with lymphoma, then ≤ 5 times)
• Aspartate aminotransferase (AST) ≤ 3 times upper limit of institutional normal (within 14 days of study registration) (unless documented Gilbert’s syndrome or liver involvement with lymphoma, then ≤ 5 times)
• Total bilirubin ≤ 3 times upper limit of institutional normal (within 14 days of study registration) (unless documented Gilbert’s syndrome or liver involvement with lymphoma, then ≤ 5 times)
• Left ventricular ejection fraction (LVEF) ≥ 35% (within 28 days of study registration)
• Participants who are of childbearing potential or have partners of child-bearing potential must agree to either total abstinence or use of both a highly effective (intrauterine device [IUD], hormonal contraceptives, tubal ligation or vasectomy), and effective contraception (male or female condom, diaphragm or cervical cap) for the duration of treatment and for 12 months after the last dose of study drug
• Able to tolerate prophylactic anticoagulation/antiplatelet therapy while on lenalidomide
• Able to provide written voluntary consent prior to the performance of any research related tests or procedures (or the subject’s legally authorized representative [LAR] if enrollment of persons with diminished capacity is permitted-general permitted for phase II and greater studies)

Exclusion Criteria

• Seropositive for or active viral infection with hepatitis B virus (HBV) as defined below: * HBV surface antigen (HBsAg) positive ** Exception: Subjects who are seropositive because of HBV vaccination are eligible (these subjects will be HBV surface antibody [anti-HBs] positive but HBV core antibody [anti-HBc] negative, and HBV surface antigen [HBsAg] negative) * HBsAg negative, anti-HBs positive and/or anti-HBc positive, and detectable viral deoxyribonucleic acid (DNA) ** Exception: Subjects who are seropositive because of a successfully treated, prior infection are eligible (HBsAg negative, anti-HBs positive, and/or anti-HBc positive, but viral DNA negative)
• Hepatitis C virus (HCV) positive subjects with chronic hepatitis C (detectable viral DNA at time of randomization), or subjects with an active hepatitis C infection requiring anti-viral medication (at time of randomization) * Exception: subjects who have a positive surface antigen or core antibody but do not have detectable viral DNA or symptoms of hepatitis C, and who are otherwise acceptable candidates for lenalidomide/ tafasitamab/rituximab chemotherapy, as documented by the investigator, are eligible
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV)
• Prior history of lenalidomide use
• Prior history of malignancies, other than follicular or marginal zone lymphoma, unless the subject has been free of the disease for ≥ 5 years. Exceptions include a history of previously treated: * Localized non-melanoma skin cancer * Carcinoma in situ of the cervix/bladder/breast * T1a or T1b of prostate cancer
• Peripheral neuropathy ≥ grade 2 at time of screening
• Uncontrolled intercurrent illness
• Active infection (requiring systemic therapy) or has received a live vaccine within 14 days prior to first dose of study drug
• Presence or history of central nervous system (CNS) involvement by lymphoma
• Patients who are not willing to take venous thromboembolic (VTE) prophylaxis or antiplatelet therapy
• Recent (< 1 year ) arterial thrombosis (any) or venous thrombosis ≥ grade 3 by Common Terminology Criteria for Adverse Events (CTCAE) 5.0
• Pregnant or breastfeeding as agents used in this study are pregnancy category X. Women of childbearing potential must have two negative pregnancy tests (serum or urine) prior to their first dose of lenalidomide, and must agree to scheduled pregnancy testing while on treatment regardless of their birth control choice, per the requirements of the lenalidomide risk evaluation and mitigation strategy (REMS) program