Biomaterial Database

A phase I/II trial combining high-dose melphalan and autologous transplant with bortezomib for multiple myeloma: a dose- and schedule-finding study. 2010

Sagar Lonial, and Jonathan Kaufman, and Mourad Tighiouart, and Ajay Nooka, and Amelia A Langston, and Leonard T Heffner, and Claire Torre, and Stephanie McMillan, and Heather Renfroe, and R Donald Harvey, and Mary J Lechowicz, and H Jean Khoury, and Christopher R Flowers, and Edmund K Waller

Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA. sloni01@emory.edu

OBJECTIVE We did a randomized phase I/II trial designed to evaluate the safety and efficacy of combining the proteasome inhibitor bortezomib with high-dose melphalan as the conditioning for high-dose therapy and autologous transplant for myeloma. METHODS Enrolled patients were limited to those who did not achieve a very good partial remission (VGPR) following one or more induction regimens, and were randomized to receive a single escalating dose of bortezomib (1.0, 1.3, or 1.6 mg/m(2)) either 24 hours before or 24 hours after high-dose melphalan. Dose escalation was based on the escalation with overdose control (EWOC), a Bayesian statistical model. Bone marrow aspirates were collected before initiation of therapy and at the time of transplant to evaluate which sequence resulted in maximal plasma cell apoptosis, and response to transplant was assessed by the International Myeloma Working Group criteria. RESULTS Among 39 randomized patients, 20 received bortezomib after melphalan and 19 received bortezomib before melphalan. Toxicities and posttransplant hematopoietic recovery rates were similar between arms. The overall response rate for all patients was 87%, with 51% achieving a VGPR or better. Pharmacodynamic studies showed greater plasma cell apoptosis among patients who received bortezomib following melphalan. CONCLUSIONS The use of bortezomib in conjunction with high-dose melphalan is safe, with data suggesting improved efficacy. A single dose of bortezomib administered after high-dose melphalan is the recommended dose and schedule for future clinical investigation.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008558	Melphalan	An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.	Medphalan,Merphalan,Phenylalanine Mustard,Sarcolysine,Sarkolysin,4-(Bis(2-chloroethyl)amino)phenylalanine,Alkeran,L-PAM,Mustard, Phenylalanine
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009101	Multiple Myeloma	A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.	Myeloma, Plasma-Cell,Kahler Disease,Myeloma, Multiple,Myeloma-Multiple,Myelomatosis,Plasma Cell Myeloma,Cell Myeloma, Plasma,Cell Myelomas, Plasma,Disease, Kahler,Multiple Myelomas,Myeloma Multiple,Myeloma, Plasma Cell,Myeloma-Multiples,Myelomas, Multiple,Myelomas, Plasma Cell,Myelomas, Plasma-Cell,Myelomatoses,Plasma Cell Myelomas,Plasma-Cell Myeloma,Plasma-Cell Myelomas
D011719	Pyrazines	A heterocyclic aromatic organic compound with the chemical formula C4H4N2.	Pyrazine
D001897	Boronic Acids	Inorganic or organic compounds that contain the basic structure RB(OH)2.	Boronic Acid,Acid, Boronic,Acids, Boronic
D003131	Combined Modality Therapy	The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.	Multimodal Treatment,Therapy, Combined Modality,Combined Modality Therapies,Modality Therapies, Combined,Modality Therapy, Combined,Multimodal Treatments,Therapies, Combined Modality,Treatment, Multimodal,Treatments, Multimodal
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005260	Female		Females