A Phase 1 Study of CCI-779 in Combination With Dexamethasone in Multiple Myeloma
I. To assess the toxicity and safety of temsirolimus in combination with dexamethasone in
patients with recurrent or refractory multiple myeloma.
II. To assess a dose of temsirolimus that is capable of inhibiting the mammalian target of
rapamycin (mTOR) in myeloma tumor cells.
I. To assess the efficacy of temsirolimus in combination with dexamethasone in these
II. To correlate the efficacy of this regimen with molecular characteristics of the
individual tumor clones.
OUTLINE: This is a multicenter, dose-escalation study of temsirolimus.
Patients receive temsirolimus intravenously (IV) over 30 minutes once weekly on days 1, 8,
15, and 22 and oral dexamethasone once on days 1, 2, 8, 9, 15, 16, 22, and 23. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo bone marrow aspiration and blood sample collection periodically for
correlative studies. Correlative studies include analysis of p70S6 kinase activity in
peripheral blood mononuclear cells and in multiple myeloma cells; analysis of the degree of
AKT phosphorylation and degree of PTEN expression in multiple myeloma cells by
immunohistochemistry; Ras mutational analysis; and Myc 5'UTR mutational analysis.
After completion of study treatment, patients are followed for 4 weeks.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of temsirolimus
The MTD is the dose level at which less than 2 out of 6 subjects experience DLT. Assessed according to the NCI Common Toxicity Criteria (CTC).
Course 1 (first 28 days)
Veterans Administration Los Angeles Healthcare System
United States: Food and Drug Administration
|Veteran's Administration Medical Center||Las Angeles, California 90073|