Phase 2, Single-arm, Open-label, Study of Loncastuximab Tesirine in Combination with Rituximab in Patients with Relapsed or Refractory Follicular Lymphoma

Eligibility: Inclusion Criteria
  •   1. Men and women >= 18 years of age.
  •   2. 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.
  •   3. 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.
  •   4. 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.
  •   5. 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
  •   6. Progression or relapse within 24 months of frontline treatment in patients previously treated with >=1 line of systemic therapy; or
  •   7. Second FL relapse/progression after >=1 line of systemic therapy. These patients will be eligible independently of GELF criteria and POD24.
  •   8. Eastern Cooperative Oncology Group (ECOG) performance status = 2.
  •   9. Life expectancy of greater than 6 weeks.
  •   10. 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
  •   1. FL grade 3B or transformed FL.
  •   2. [Removed]
  •   3. >= 6 lines of systemic immunochemotherapy for treatment of FL.
  •   4. Patients with clinically significant pleural effusions and/or ascites requiring drainage or associated with shortness of breath.
  •   5. Patients receiving any other investigational agents.
  •   6. Patients with known central nervous system involvement of lymphoma.
  •   7. 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).
  •   8. Breastfeeding or pregnant women.
  •   9. 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.
  •   10. History of Human immunodeficiency virus (HIV) infection. Note: HIV screening test is optional
  •   11. Patients with impaired decision-making capacity.