A Pilot Study of Low Dose Melphalan and Bortezomib for Treatment of Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndromes
In patients who develop acute myelogenous leukemia (AML) or a high-risk myelodysplastic
syndrome (MDS), the current standard treatment involves multidrug induction chemotherapy
utilizing an anthracycline or anthraquinone with cytarabine. While chemotherapy has proven
effective at inducing remission in up to 90% of patients, elderly patients fair far worse.
In patients over the age of sixty, the disease is not only less responsive to therapy, but
an increased number of comorbid conditions makes induction therapy a more dangerous
endeavor. Because of this, many patients are not offered standard induction chemotherapy and
there is a dearth of viable alternatives for treatment of these otherwise fatal diseases.
Low dose melphalan has previously been shown to be an effective palliative treatment for
patients diagnosed with AML and high-risk MDS. It was found to have an overall response rate
of 40% in AML patients (30% complete remission and 10% partial remission) and a 57% overall
response in high-risk MDS patients (33% complete remission, 5% partial remission, and 19%
minor responses). This therapy, while not curative, is one of the few options for patients
unable to tolerate more intensive treatment regimens, but desiring a potentially effective
Bortezomib (VELCADE®) is an intravenously administered reversible, selective inhibitor of
the 26S proteosome. Although all of the mechanisms by which this novel drug acts as an
antineoplastic agent are not fully understood, in vivo and in vitro studies indicate they
ultimately result in the inhibition of the gene expression necessary for cell growth and
survival pathways, apoptotic pathways, and cellular adhesion, migration, and angiogenesis
Preclinical and clinical evaluation of the combination of melphalan and bortezomib has
demonstrated impressive synergy in refractory multiple myeloma cell lines and patients with
myeloma. This study aims to determine if these findings hold true in AML and MDS patients.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine response rate of the combination of bortezomib and melphalan in patients with AML and high-risk MDS.
Marc Gautier, MD
Dartmouth-Hitchcock Medical Center
United States: Institutional Review Board
|Dartmouth-Hitchcock Medical Center||Lebanon, New Hampshire 03756|
|Integrated Community Oncology Network||Jacksonville Beach, Florida 32250|