Lenalidomide and Temsirolimus in Treating Patients With Previously Treated Multiple Myeloma
|ClinicalTrials.gov Identifier: NCT00398515|
Recruitment Status : Completed
First Posted : November 10, 2006
Last Update Posted : September 30, 2013
|Condition or disease||Intervention/treatment||Phase|
|Refractory Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma||Drug: lenalidomide Drug: temsirolimus Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
I. Determine the maximum tolerated dose of CCI-779 (temsirolimus) when given together with lenalidomide in patients with previously treated multiple myeloma.
I. Determine the toxicity of this regimen in these patients. II. Determine the clinical response of patients treated with this regimen. III. Determine the pharmacokinetics of this regimen. IV. Determine the pharmacodynamic effects of this regimen in these patients. V. Determine the effect of this regimen on immunological cellular and serological parameters and hematopoietic precursor cells.
OUTLINE: This is a dose-escalation study of CCI-779.
Patients receive temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22 and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Patients achieving at least a partial response after 12 courses may continue to receive CCI-779 and lenalidomide as above in the absence of disease progression. Cohorts of 3 patients receive escalating doses of CCI-779 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Ten patients are treated at the MTD. Patients undergo blood sample and bone marrow collection periodically during study treatment for pharmacokinetic and pharmacodynamic studies, and to determine the immunomodulatory effects of CCI-779 and lenalidomide.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of CC-5013 (Lenalidomide) and CCI-779 in Patients With Relapsed or Refractory Multiple Myeloma|
|Study Start Date :||March 2007|
|Primary Completion Date :||February 2012|
U.S. FDA Resources
Experimental: Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)
Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: temsirolimus
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
- Maximum tolerated dose (MTD) of temsirolimus when given together with lenalidomide [ Time Frame: Course 1 (first 28 days) ]The MTD is the dose level at which less than 2 out of 6 patients experience dose limiting toxicities (DLT). The National Cancer Institute Common Terminology Criteria for Adverse events (CTCAE) version 3.0 will used to characterize toxicities.
- Toxicity of lenalidomide and temsirolimus combination therapy in previously treated mulple myeloma patients [ Time Frame: From the time of their first treatment with lenalidomide and temsirolimus ]Measured by NCI CTCAE version 3.0.
- Pharmacokinetic analysis of lenalidomide [ Time Frame: Baseline and days 1 and 22 (lenalidomide only) of course 1 ]Plasma drug levels will be measured by liquid chromatography and tandem mass spectroscopy.
- Pharmacodynamics of temsirolimus in peripheral blood mononuclear cells (PBMC) [ Time Frame: Days 1 and 8 of course 1 ]PBMC will be used to assess the phosphorylation status of p70S6K to evaluate the pharmacodynamic activity of each dose level. This will assist in determining the biologically active dose in the event that dose limiting toxicity is not observed. The analysis of p70^S6K and phospho (P)-p70^S6K will be assessed by Western blotting using specific antibodies. The expression level will be quantified by densitometry. The inhibition of P- p70S6K will be correlated with clinical endpoints and PK parameters.
- Assessment of serum cytokines; IL-2, sIL-2R, TNF-alpha, IFN-gamma, IL-1 beta, IL-1Ra, GM-CSF, IL-8, IL-6, sIL-6R, MIP-1 alpha, VEGF, and b-FGF [ Time Frame: Baseline and then every 4 weeks ]Assessed by ELISA.
- Assessment of peripheral blood immune cell subsets [ Time Frame: Baseline and then every 4 weeks ]We will investigate immune cell subsets by flow-cytometry.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00398515
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Craig Hofmeister||Ohio State University|