A Phase I/II Study of Escalating Doses of Thalidomide in Conjunction With Bortezomib and HIgh Dose Melphalan as a Conditioning Regimen for Autologous Peripheral Blood Stem Cell Transplantation in Patients With Advanced Multiple Myeloma
VELCADE™ (bortezomib) for Injection is a small molecule proteasome inhibitor developed by
Millennium Pharmaceuticals, Inc., (Millennium) as a novel agent to treat human malignancies.
VELCADE is currently approved by the United States Food and Drug Administration (US FDA) and
it is registered in Europe for the treatment of multiple myeloma patients who have received
at least one prior therapy.
By inhibiting a single molecular target, the proteasome, bortezomib affects multiple
signaling pathways. The anti-neoplastic effect of bortezomib likely involves several
distinct mechanisms, including inhibition of cell growth and survival pathways, induction of
apoptosis, and inhibition of expression of genes that control cellular adhesion, migration
and angiogenesis. Thus, the mechanisms by which bortezomib elicits its antitumor activity
may vary among tumor types, and the extent to which each affected pathway is critical to the
inhibition of tumor growth could also differ. Bortezomib has a novel pattern of cytotoxicity
in National Cancer Institute (NCI) in vitro and in vivo assays (Adams et al., 1999). In
addition, bortezomib has cytotoxic activity in a variety of xenograft tumor models, both as
a single agent and in combination with chemotherapy and radiation (Steiner et al., 2001;
Teicher et al., 1999; Cusack et al., 2001; LeBlanc et al., 2002; Pink et al., 2002).
Notably, bortezomib induces apoptosis in cells that over express bcl-2, a genetic trait that
confers unregulated growth and resistance to conventional chemotherapeutics (McConkey et
al., 1999).
Bortezomib is thought to be efficacious in multiple myeloma via its inhibition of nuclear
factor κB (NF-κB) activation, its attenuation of interleukin-6 (IL-6)-mediated cell growth,
a direct apoptotic effect, and possibly anti-angiogenic and other effects.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the maximum tolerated dose of thalidomide used in conjunction with dose-intense melphalan, bortezomib and autologous (syngeneic) HSC support in the salvage therapy of patients who failed a prior treatment with dose-intense melphalan
Determine the maximum tolerated dose of thalidomide used in conjunction with dose-intense melphalan, bortezomib and autologous (syngeneic) HSC support in the salvage therapy of patients who failed a prior treatment with dose-intense melphalan
Dose escalation will be based on the assessment of tolerability determined after the last patient of each cohort reaches day +21.
Yes
Scott D Rowley, MD
Principal Investigator
John Theurer Cancer Center at Hackensack Univ Medical Center
United States: Food and Drug Administration
PRO-00001215
NCT01242267
April 2010
December 2014
Name | Location |
---|---|
John Theurer Cancer Center at Hackensack University Medical Center | Hackensack, New Jersey 07601 |