A Prospective Open-Label Pilot Trial of PS-341 (Bortezomib; VELCADE) for the Therapy of Symptomatic Advanced Myeloproliferative Disorders
- Determine the efficacy of bortezomib in patients with symptomatic advanced
myeloproliferative disorders (i.e., myelofibrosis with myeloid metaplasia, chronic
myelomonocytic leukemia, or FIP1LI-PDGFRA-negative mast cell disease).
- Determine the safety of this drug when administered on a modified schedule in these
- Determine the effect of this drug on bone marrow cellularity, tryptase-positive mast
cells, reticulin fibrosis, osteosclerosis, and angiogenesis in responding patients
OUTLINE: This is a prospective, open-label, pilot, multicenter study. Patients are
stratified according to disease (systemic mast cell disease vs chronic myelomonocytic
leukemia vs myelofibrosis with myeloid metaplasia).
Patients receive bortezomib IV weekly for 4 weeks. Treatment repeats every 5 weeks for up to
2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving
a response (complete remission, partial remission, or minimal remission) after 2 courses may
receive an additional 6 courses of therapy. Patients who achieve stable disease with
acceptable toxicities after 2 courses receive bortezomib IV at a higher dose twice weekly
for 2 weeks. Treatment with a higher dose of bortezomib repeats every 3 weeks for up to 6
Patients who are responders undergo bone marrow aspirate or biopsy and peripheral blood
collection for evaluation of bone marrow cellularity, tryptase-positive mast cells,
reticulin fibrosis, osteosclerosis, and angiogenesis by fluorescent in situ hybridization
(FISH), immunohistochemistry, and other immunological laboratory methods.
After completion of study therapy, patients are followed periodically for up to 3 years.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Number and severity of toxicities as assessed by NCI CTCAE v3.0
Ruben A. Mesa, M.D.
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|M. D. Anderson Cancer Center at University of Texas||Houston, Texas 77030-4009|
|Mayo Clinic in Florida||Jacksonville, Florida 32224|