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A Phase I Trial of CC-5013 (Lenalidomide) and CCI-779 in Patients With Relapsed or Refractory Multiple Myeloma

Phase 1
18 Years
Open (Enrolling)
Refractory Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

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Trial Information

A Phase I Trial of CC-5013 (Lenalidomide) and CCI-779 in Patients With Relapsed or Refractory Multiple Myeloma


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.

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

- 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

- 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

- 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

- No concurrent grapefruit or grapefruit juice

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) of temsirolimus when given together with lenalidomide

Outcome Description:

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.

Outcome Time Frame:

Course 1 (first 28 days)

Safety Issue:


Principal Investigator

Craig Hofmeister

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University


United States: Food and Drug Administration

Study ID:




Start Date:

March 2007

Completion Date:

Related Keywords:

  • Refractory Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Ohio State University Medical Center Columbus, Ohio  43210