Lenalidomide and Temsirolimus in Treating Patients With Previously Treated Multiple Myeloma
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00398515 |
Recruitment Status
:
Completed
First Posted
: November 10, 2006
Last Update Posted
: September 30, 2013
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of CCI-779 (temsirolimus) when given together with lenalidomide in patients with previously treated multiple myeloma.
SECONDARY OBJECTIVES:
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) |
Primary Purpose: | Treatment |
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 |
Actual Primary Completion Date : | February 2012 |

Arm | Intervention/treatment |
---|---|
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.
|
Drug: lenalidomide
Given orally
Other Names:
Drug: temsirolimus
Given IV
Other Names:
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
|
- 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-
Diagnosis of multiple myeloma (MM)
- Salmon-Durie stage IIA or IIIA
- No stage B disease
-
Meets ≥ 1 major AND 1 minor criterion OR ≥ 3 minor criteria
-
The following are considered major criteria:
- Plasmacytoma on tissue biopsy
- Bone marrow plasmacytosis with ≥ 30% plasma cells
- Monoclonal paraprotein ≥ 3,500 mg/dL (IgG) or ≥ 2,000 mg/dL (IgA) OR monoclonal protein (Bence-Jones protein) ≥ 1,000 mg by 24-hour urine collection
-
The following are considered minor criteria:
- Bone marrow plasmacytosis 10-29% of marrow cellularity
- Monoclonal globulin spike < 3,500 mg/dL (IgG) or < 2,000 mg/dL (IgA)
- Lytic bone lesions
- Decrease in normal IgM (< 50 mg/dL), IgA (< 100 mg/dL), or IgG (< 600 mg/dL)
-
- Disease progression after ≥ 1 prior systemic treatment regimen* for MM (e.g., chemotherapy, high-dose corticosteroids, thalidomide, or bortezomib), defined as > 25% increase in serum or urine M-protein
- No solitary plasmacytoma
- No non-secretory MM (absent serum or urinary M-protein)
- ECOG performance status 0-2
- Life expectancy > 6 months
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 3 times ULN
- Creatinine ≤ 2.0 mg/dL
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Fasting cholesterol ≤ 350 mg/dL
- Fasting triglycerides ≤ 400 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception
- Must agree not to donate blood, sperm, or ova during and for 4 weeks after completion of study treatment
-
No other prior or concurrent malignancy or myelodysplasia except for the following:
- Basal cell or squamous cell skin cancer
- Carcinoma in situ of the cervix
- Localized cancer treated with surgery only with no evidence of disease for > 5 years
-
No history of recurrent deep vein thrombosis (DVT)/pulmonary embolism (PE) or DVT/PE occurring while on therapeutic levels of anticoagulation
- Patients with DVT/PE within the past 6 months are eligible provided they receive full anticoagulation during study treatment
- No active infection requiring oral or intravenous antibiotics
-
No uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would preclude study compliance
- No known hepatitis B or C
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide or CCI-779
- See Disease Characteristics
- Prior lenalidomide allowed
- Prior high-dose chemotherapy with stem cell transplantation allowed
- More than 4 weeks since prior chemotherapy or other antimyeloma systemic therapy (e.g., thalidomide, bortezomib, or high-dose corticosteroids) and recovered
-
No prior exposure to both lenalidomide and mTOR inhibitors (given together)
- Treatment with single-agent lenalidomide or single-agent mTOR inhibitor allowed
- No other concurrent investigational agents
- No concurrent corticosteroids unless for physiologic maintenance
- No concurrent antiretroviral therapy for HIV-positive patients
- No concurrent myeloid growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])
- No concurrent grapefruit or grapefruit juice

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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 |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00398515 History of Changes |
Obsolete Identifiers: | NCT01645553, NCT01664442 |
Other Study ID Numbers: |
NCI-2009-00151 NCI-2009-00151 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) OSU-2006C0040 CDR0000514831 OSU-05115 05115 ( Other Identifier: Ohio State University Medical Center ) 7314 ( Other Identifier: CTEP ) U01CA076576 ( U.S. NIH Grant/Contract ) |
First Posted: | November 10, 2006 Key Record Dates |
Last Update Posted: | September 30, 2013 |
Last Verified: | September 2013 |
Additional relevant MeSH terms:
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Lenalidomide |
Thalidomide Everolimus Sirolimus Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents Immunosuppressive Agents Leprostatic Agents Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic |