Phase II Study of PS341 (VELCADE) in Myelodysplastic Syndromes (MDS). EudraCT Number 2004-002935-23
The Myelodysplastic Syndromes (MDS) are an heterogeneous group of clonal disorders of the
hematopoietic stem cell characterized by ineffective hematopoiesis leading to peripheral
cytopenias, and variable risk of progression to more advanced disease and/or transformation
to acute myeloid leukemia (AML). The disease affects predominantly elderly individuals
(median age 69 years); the overall incidence is about 4 per 100,000 individuals but this
rises to > 30 per 100,000 in the over 70 year age population.
Therapy for MDS has included hematopoietic growth factors (in primis EPO, in combination or
not with granulocyte-colony stimulating factor- G-CSF or granulocyte-colony stimulating
factor-GM-CSF), differentiating agents, immunotherapy, low dose chemotherapy strategies,
AML-like induction regimens, traditional cytotoxic agents, and hematopoietic stem cell
transplantation (HSCT) strategies. With the exception of HSCT, which can result in long-term
survival in 23% to 50% of patients (Ref. 10) therapy for MDS has not consistently shown a
survival advantage, and also modest results have been obtained in an attempt to improve
anemia and/or the other cytopenias, and to decrease the number of red blood cell (RBC)
transfusions. Furthermore, MDS is primarily a disease of older patients who cannot tolerate
aggressive therapy and therefore cannot receive HSCT.
No therapy has thus been considered standard for MDS, and supportive therapy, including RBC
transfusions, platelet transfusions and antibiotic therapy has often been focus of care,
especially in the older patient population.
VELCADE™ (bortezomib) for injection is a small molecule proteasome inhibitor developed by
Millennium Pharmaceuticals, Inc., (MPI) as a novel agent to treat human malignancies.
VELCADE is currently approved by the US FDA for the treatment of multiple myeloma patients
who have received at least 2 prior therapies and have demonstrated disease progression on
the last therapy. VELCADE is a modified dipeptidyl boronic acid derived from leucine and
phenylalanine; its chemical name is N pyrazinecarbonyl L phenylalanine L leucine boronic
acid and has a molecular weight of 384.25 daltons.
Data from non clinical and clinical studies conducted to date support the development of
Velcade for the treatment of human malignancies.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
to determine activity of Velcade in patients with MDS, intermediate-2 or high risk, and intermediate-1 or low risk unresponsive or not eligible for treatment with erythropoietin or immunosuppressive agents as assessed according to response criteria.
Giuliana ALIMENA, MD, PHD
Università degli Studi di Roma "La Sapienza", Dipartimento di Biotecnologie Cellulari ed Ematolgia
Italy: The Italian Medicines Agency