Lenalidomide and Temsirolimus in Treating Patients With Previously Treated Multiple Myeloma

NCT00398515 | Completed Phase 1

• 7 other identifiers: NCI-2009-00151OSU-2006C0040CDR0000514831OSU-05115051157314U01CA076576
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of temsirolimus when given together with lenalidomide in treating patients with previously treated multiple myeloma. Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Drugs used in chemotherapy, such as temsirolimus, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temsirolimus may also stop the growth of cancer cells by blocking some of the enzymes needed for their growth. Giving lenalidomide together with temsirolimus may kill more cancer cells.

Conditions

Refractory Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

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

  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.

  Course 1 (first 28 days)

Secondary Outcomes (5)

• Toxicity of lenalidomide and temsirolimus combination therapy in previously treated mulple myeloma patients

  From the time of their first treatment with lenalidomide and temsirolimus

• Pharmacokinetic analysis of lenalidomide

  Baseline and days 1 and 22 (lenalidomide only) of course 1

• Pharmacodynamics of temsirolimus in peripheral blood mononuclear cells (PBMC)

  Days 1 and 8 of course 1

• 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

  Baseline and then every 4 weeks

• Assessment of peripheral blood immune cell subsets

  Baseline and then every 4 weeks

Study Arms (1)

Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)

EXPERIMENTAL

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; Drug: temsirolimus; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

lenalidomide DRUG

Given orally

Also known as: CC-5013, IMiD-1, Revlimid

Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)

temsirolimus DRUG

Given IV

Also known as: CCI-779, cell cycle inhibitor 779, Torisel

Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; temsirolimus; Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Macrolides; Lactones

Study Officials

• Craig Hofmeister

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2006
• First Posted: November 10, 2006
• Study Start: March 1, 2007
• Primary Completion: February 1, 2012
• Last Updated: September 30, 2013

Record last verified: 2013-09

Locations

US (1)