Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

DLBCL is an aggressive malignant disease which evolves from B-cells and affects mainly the lymphatic tissue. Due to its aggressive nature the disease is characterized by a fast course which is lethal without therapy. Potentially curative therapy options are available even at advanced stages. Standard-first line leads to a high initial response rate (85-90%) and an approximate cure rate of 50% of patients. Patients refractory to or with early relapse after this treatment (10-15%) have a very poor prognosis. Blinatumomab is a bispecific single-chain antibody derivative against CD19 and CD3, designed to link B-cells and T-cells resulting in T-cell activation and a cytotoxic T-cell response against CD19 expressing cells. This study consisted of a screening period, treatment period, and a follow-up efficacy and survival period. The core study comprises the treatment period to the 30 days after the last infusion. The first cycle consisted of a continuous intravenous (CIV) infusion over 8 weeks. Participants who achieved a Complete Response (CR) or Partial Response (PR) or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval. After the last treatment cycle, efficacy and survival follow-up visits occurred for up to 24 months from treatment start. Participants who relapsed during the follow-up period may have received an additional 8 weeks of treatment. Two dose regimens were assessed in this study. Stage 1 comprised 2 dose cohorts. In Cohort 1, the first 6 participants were to receive blinatumomab in a dose-escalating manner: 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. In Cohort 2, the next 6 participants enrolled were to receive a constant dose of 112 µg/day blinatumomab. Before the initiation of stage 2, a pre-planned data monitoring committee (DMC) meeting was held to assess the safety profile of Cohort 1 and Cohort 2. The dosing regimen with the more favorable benefit-risk profile was to be selected for Cohort 3.