Loncastuximab Tesirine in Combination With Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma

Inclusion criteria

• Men and women ≥ 18 years of age.
• Patients must have histologic confirmation of Follicular Lymphoma (FL) (grade 1, 2 and 3A). Note: Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy.
• Patients with relapsed or refractory FL previously treated with ≥1 line of systemic therapy having ≥ 1 Groupe d'Etude des Lymphomes (GELF) criteria for therapy, or Progression of Diseases within 24 months (POD24), or second relapse.
• Baseline FDG-PET/CT scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites. Patients should have at least one measurable site of disease per Lugano classification.
• Patient should have ≥ 1 Groupe d'Etude des Lymphomes (GELF) criteria for treatment initiation).

• Involvement of ≥3 nodal sites, each with diameter of ≥3 cm
• Any nodal or extranodal tumor mass with a diameter of ≥7 cm
• B symptoms (fever ≥ 38 degrees Celsius of unclear etiology, night sweats, weight loss > 10% within the prior 6 months).
• Risk of local compressive symptoms that may result in organ compromise
• Splenomegaly or splenic lesion without splenomegaly
• Leukopenia (leukocytes < 1000/mm3)
• Leukemia (> 5.000 lymphoma cells/mm3)
• Bone lesions detected on FDG-PET/CT; or
• Progression or relapse within 24 months of frontline treatment in patients previously treated with ≥1 line of systemic therapy; or
• Second FL relapse/progression after ≥1 line of systemic therapy. These patients will be eligible independently of GELF criteria and POD24.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Life expectancy of greater than 6 weeks.
• Patients must have normal organ and marrow function as defined below,

• Absolute neutrophil count ≥1000/mm3 (unless due to lymphoma involvement of the bone marrow or spleen).
• Platelets ≥100,000/mm3 or ≥ 60,000/mm3 in case of bone marrow involvement by lymphoma.
• Hemoglobin ≥ 10 g/dL or ≥8 g/dL in case of bone marrow involvement by lymphoma.
• Total bilirubin < 1.5 x within normal institutional limits (unless due to lymphoma involvement of liver or a known history of Gilbert's disease).
• Gamma-Glutamyl Transpeptidase (GGT)/Aspartate Aminotransferase (AST)/(SGOT)/Alanine Aminotransferase (ALT)(SGPT) ≤ 2.5 × institutional upper limit of normal.
• Creatinine within normal institutional limits, or creatinine clearance ≥30 ml/min/1.7m^2 for patients with creatinine levels above institutional normal (unless due to lymphoma).

Exclusion criteria

• FL grade 3B or transformed FL.
• [Removed]
• ≥ 6 lines of systemic immunochemotherapy for treatment of FL.
• Patients with clinically significant pleural effusions and/or ascites requiring drainage or associated with shortness of breath.
• Patients receiving any other investigational agents.
• Patients with known central nervous system involvement of lymphoma.
• Uncontrolled intercurrent illness such as: history of Myocardial Infarction (MI) in the last 6 months, congestive heart failure New York Heart Association (NYHA) Class III-IV, uncontrolled or symptomatic arrhythmia, stroke in last 6 months, liver cirrhosis, and autoimmune disorder requiring immunosuppression or long-term corticosteroids (>10 mg daily prednisone equivalent).
• Breastfeeding or pregnant women.
• Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody will need a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.) Hepatitis C antibody positive patients are eligible if PCR is negative. Hepatitis B core antibody (+) patients without evidence of HBsAg or Hep B PCR (+) are eligible with appropriate Hepatitis B reactivation prophylaxis.
• History of Human immunodeficiency virus (HIV) infection. Note: HIV screening test is optional
• Patients with impaired decision-making capacity.