Date: 2014-05-19
Type of information: Results
phase: 3
Announcement: results
Company: Genmab (Denmark) GSK (UK)
Product: ofatumumab
Action
mechanism: Ofatumumab is a human monoclonal antibody which targets an epitope in the CD20 molecule encompassing parts of the small and large extracellular loops,
Disease: diffuse large B-cell lymphoma (DLBCL)
Therapeutic area: Cancer Oncology
Country: Austria, Belgium, China, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, India, Ireland
Trial
details: Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (ORCHARRD) is being conducted to compare the efficacy and safety of ofatumumab in addition to salvage chemotherapy versus rituximab in addition to salvage chemotherapy in CD20 positive DLBCL subjects relapsing, or with persistent disease, after first-line treatment with rituximab combined with an anthracycline-based chemotherapy regimen and be eligible for autologous stem cell transplant (ASCT). (NCT01014208) The study included 447 patients. Patients in the study were randomized 1:1 to receive three cycles of either ofatumumab or rituximab in combination with DHAP (dexamethasone, cytarabine and cisplatin) salvage chemotherapy. After the third treatment cycle, patients who obtained a complete or partial response received high dose chemotherapy followed by ASCT. The primary endpoint of the study was progression free survival. The ORCHARRD study was conducted in collaboration with the following research groups: HOVON-Dutch-Belgian Cooperative Trial Group for Hematology-Oncology, Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea (GELTAMO), National Cancer Research Institute Lymphoma Clinical Studies Group, Nordic Lymphoma Group, Polish Lymphoma Research Group, The All Ireland Cooperative Oncology Research Group.
Latest
news: * On May 19, 2014, GSK and Genmab announced that the Phase III study (ORCHARRD) of ofatumumab (Arzerra™) plus chemotherapy versus rituximab plus chemotherapy to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) did not meet its primary endpoint as there was no statistically significant difference in progression free survival (PFS) between the treatment arms. There were no differences in adverse events (AEs) leading to treatment discontinuation, Grade ≥3 AEs, severe adverse events (SAEs) or fatal SAEs between the treatment arms. However, there were more dose interruptions and delays due to infusion reactions and increased serum creatinine in the ofatumumab plus chemotherapy arm, which require further analysis. Detailed data from the ofatumumab ORCHARRD study in DLBCL will be submitted for presentation at a medical conference later this year. * On March 19, 2012, Genmab has announced the submission of a protocol amendment for the ofatumumab Phase III head-to-head study in diffuse large B-cell lymphoma (DLBCL) to regulatory authorities. According to the amended protocol all patients recruited in the study which investigates ofatumumab plus chemotherapy versus rituximab plus chemotherapy in relapsed or refractory DLBCL, will receive the same chemotherapy regimen (DHAP). The study now includes 410 patients who are refractory to or have relapsed following first line treatment with rituximab in combination with a chemotherapy regimen containing anthracycline and are eligible for autologous stem cell transplant (ASCT). Patients in the study will be randomized to receive three cycles of either ofatumumab or rituximab in addition to DHAP chemotherapy. After the third treatment cycle patients who obtain a complete or partial response will receive high dose chemotherapy followed by ASCT. The primary endpoint of the study is progression free survival. This change will revise underlying timing assumptions in the study and could bring forward the primary endpoint analysis to early 2014. In the United States and Europe , ofatumumab is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab. The effectiveness of ofatumumab is based on the demonstration of durable objective responses. No data demonstrate an improvement in disease-related symptoms or increased survival. Ofatumumab can cause serious infusion reactions, prolonged and severe cytopenias, Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, and Hepatitis B infection and reactivation.
