Temsirolimus and Dexamethasone in Treating Patients With Recurrent or Refractory Multiple Myeloma

NCT00693433 | Completed Phase 1

• 3 other identifiers: NCI-2009-00157VAMC-SC-7353CDR0000597181
• Study Type: interventional
• Target: 15
• 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 dexamethasone in treating patients with recurrent or refractory multiple myeloma. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus together with dexamethasone may kill more cancer cells.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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)

• Toxicity and safety

  The description and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting.

  Continuously from start of treatment study

Secondary Outcomes (5)

• Correlation between response to treatment with temsirolimus and the degree of p70 inhibition in peripheral blood mononuclear cells and in multiple myeloma (MM) cells

  Every 4 weeks

• Correlation between response to treatment with temsirolimus and the degree of pre-treatment AKT activation in MM cells

  Every 4 weeks

• Correlation between response to treatment with temsirolimus and the degree of PTEN expression in MM cells

  Every 4 weeks

• Correlation between response to treatment with temsirolimus and the presence of RAS mutations

  Every 4 weeks

• Correlation between response to treatment with temsirolimus and the presence of myc mutations

  Every 4 weeks

Study Arms (1)

Treatment (enzyme inhibitor, chemotherapy)

EXPERIMENTAL

Patients receive temsirolimus 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.

Drug: dexamethasone; Drug: temsirolimus; Other: laboratory biomarker analysis

Interventions

dexamethasone DRUG

Given orally

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Treatment (enzyme inhibitor, chemotherapy)

temsirolimus DRUG

Given IV

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

Treatment (enzyme inhibitor, chemotherapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor, chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed multiple myeloma
• Measurable levels of M protein in serum and/or urine
• Recurrent or refractory disease
• Progressive disease after treatment with ≥ 2 separate chemotherapeutic regimens
• At least 1 of the regimens must have included high-dose dexamethasone (40 mg on days 1-4, 9-12, and 17-20) or medium-dose dexamethasone (40 mg on days 1, 8, 15, and 22) of a 28-day course
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy ≥ 8 weeks
• Absolute neutrophil count \> 1,000/mm\^3
• Platelet count \> 100,000/mm \^3
• Total bilirubin \< 2 mg/dL
• AST and ALT \< 3 times upper limit of normal
• Creatinine \< 2 mg/dL
• Fasting cholesterol \< 350 mg/dL
• Fasting triglycerides \< 400 mg/dL
• Not pregnant or nursing

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Veteran's Administration Medical Center

Las Angeles, California, 90073, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; 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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Macrolides; Lactones

Study Officials

• Alan Lichtenstein

  Veterans Administration Los Angeles Healthcare System

  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: June 6, 2008
• First Posted: June 9, 2008
• Study Start: December 1, 2008
• Primary Completion: August 1, 2010
• Last Updated: December 4, 2015

Record last verified: 2013-06

Locations

US (1)