A Phase I/IIA Study of Carfilzomib plus High-Dose Melphalan Before Autologous Stem Cell Transplant in Patients with Multiple Myeloma

Autologous stem cell transplantation — removing some of a patient’s own stem cells before chemotherapy and returning them afterward, to re-establish a new immune and blood-forming system — is a therapy for multiple myeloma. High doses of the chemotherapy drug melphalan are traditionally used for this treatment, but in many patients the myeloma returns.

The purpose of this study is to see if giving the investigational drug carfilzomib in combination with melphalan is a safe and effective preparation for autologous stem cell transplantation in patients with multiple myeloma that has returned following or has stopped responding to standard treatment. Doctors hope that adding carfilzomib will reduce the risk of myeloma recurrence more than melphalan alone. Prior studies have shown that carfilzomib is safe and is active against myeloma.

Carfilzomib is a proteasome inhibitor. The proteasome breaks down proteins that are no longer useful to a cell. Proteasome inhibitors turn off the proteasome, causing the proteins to build up in the cell and resulting in cell death. Myeloma cells require a lot of proteins and an active proteasome to survive, so drugs that turn off the proteasome may inhibit myeloma growth.