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

NCT ID: NCT00693433

Last Updated: 2015-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31

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.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the toxicity and safety of temsirolimus in combination with dexamethasone in patients with recurrent or refractory multiple myeloma.

II. To assess a dose of temsirolimus that is capable of inhibiting the mammalian target of rapamycin (mTOR) in myeloma tumor cells.

SECONDARY OBJECTIVES:

I. To assess the efficacy of temsirolimus in combination with dexamethasone in these patients.

II. To correlate the efficacy of this regimen with molecular characteristics of the individual tumor clones.

OUTLINE: This is a multicenter, dose-escalation study of temsirolimus.

Patients receive temsirolimus intravenously (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.

Patients undergo bone marrow aspiration and blood sample collection periodically for correlative studies. Correlative studies include analysis of p70S6 kinase activity in peripheral blood mononuclear cells and in multiple myeloma cells; analysis of the degree of AKT phosphorylation and degree of PTEN expression in multiple myeloma cells by immunohistochemistry; Ras mutational analysis; and Myc 5'UTR mutational analysis.

After completion of study treatment, patients are followed for 4 weeks.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (enzyme inhibitor, chemotherapy)

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.

Group Type: EXPERIMENTAL

dexamethasone

Intervention Type: DRUG

Given orally

temsirolimus

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

dexamethasone

Given orally

Intervention Type: DRUG

temsirolimus

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Aeroseb-Dex; Decaderm; Decadron; DM; DXM; CCI-779; cell cycle inhibitor 779; Torisel

Eligibility Criteria

Inclusion Criteria

• 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
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to temsirolimus or dexamethasone
• No concurrent uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection
• Poorly controlled hypertension
• Diabetes mellitus
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situation that would limit compliance with study requirements
• See Disease Characteristics
• At least 4 weeks since prior cytotoxic therapy
• More than 4 weeks since prior chemotherapy and recovered
• No concurrent anticonvulsive or antiarrhythmic medications
• No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital) or other CYP3A4 inhibitors or inducers (e.g., rifampin or Hypericum perforatum [St. John wort])
• No concurrent prophylactic hematopoietic colony-stimulating factors
• No other concurrent investigational therapy
• No other concurrent anticancer therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alan Lichtenstein

Role: PRINCIPAL_INVESTIGATOR

Veterans Administration Los Angeles Healthcare System

Locations

Veteran's Administration Medical Center

Las Angeles, California, United States

Countries

United States

Other Identifiers

VAMC-SC-7353

Identifier Type: -

Identifier Source: secondary_id

CDR0000597181

Identifier Type: -

Identifier Source: secondary_id

NCI-2009-00157

Identifier Type: -

Identifier Source: org_study_id