Bayer HealthCare and Genzyme, in collaboration with Health Canada, informed of important safety information regarding the use of MabCampath ( Alemtuzumab ) as consolidation therapy following combination treatment with other chemotherapeutic or biologic agents.
MabCampath is a recombinant humanized monoclonal antibody and is currently authorized for the treatment of B-cell chronic lymphocytic leukemia ( B-CLL ) in patients who had been treated with alkylating agents and who have failed Fludarabine ( Fludara ) therapy.
MabCampath is not authorized for use as consolidation therapy.
Preliminary safety information from the CALGB10101 clinical trial conducted in the United States, reported six infection-related deaths out of 51 patients who received three chemotherapeutic agents ( Fludarabine + Rituximab followed by consolidation therapy with Alemtuzumab ).
The potential for an increased risk of infection-related complications may exist following treatment with multiple chemotherapeutic or biological agents.
The phase II CALGB10101 clinical trial is an ongoing study investigating the administration of induction chemotherapy with Fludarabine + Rituximab followed by Alemtuzumab for remission consolidation in previously untreated symptomatic B-CLL patients.
The induction regimen in this study consisted of Fludarabine 25 mg/m² intravenously ( IV ) on days 1-5; Rituximab escalated from 50 mg/m² on day 1 to 325 mg/m² on day 3, to 375 mg/m² on day 5 ( cycle 1 ) and then 375 mg/m² IV on day 1 of cycles 2-6; every 28 days for up to 6 cycles.
Approximately four months after the last dose of Fludarabine, patients with stable or responsive disease were to receive consolidation therapy with subcutaneous Alemtuzumab 3 mg on day 1, 10 mg on day 3, 30 mg on day 5, and 30 mg three times weekly thereafter for 6 weeks.
This study reported six infection-related deaths out of 51 patients who received the three chemotherapeutic agents ( Fludarabine + Rituximab induction and consolidation with Alemtuzumab ). The six fatal infections were reported as: viral meningitis, Listeria meningitis, Legionella pneumonia, cytomegalovirus ( CMV ) infection, Pneumocystis jiroveci pneumonia ( PCP ), and Epstein Barr Virus (EBV) associated lymphoproliferative disorder.
Bayer HealthCare and Genzyme were also informed of an additional non-infection related fatality, believed to be transfusion associated graft versus host disease ( TAGVHD ), which occurred in a non-lymphopenic patient who had received non-irradiated blood products.
Source: Health Canada, 2008