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Refractory Multiple MyelomaPhase 1NCT00693433

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

A Phase 1 study testing dexamethasone, temsirolimus and laboratory biomarker analysis in people with Refractory Multiple Myeloma and Stage I Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
dexamethasone, temsirolimus and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
Dec 2008to Aug 2010
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%
Show all 34Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Veteran's Administration Medical Center

    Las Angeles, California, 90073

Other trials in United States

About this study

Official title: A Phase 1 Study of CCI-779 in Combination With Dexamethasone in Multiple Myeloma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
dexamethasone, temsirolimus, laboratory biomarker analysis
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, DM

    Given orally

  • temsirolimusDrug

    Also called CCI-779, cell cycle inhibitor 779, Torisel

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00693433
Study groupRoleWhat they receive
Treatment (enzyme inhibitor, chemotherapy)ExperimentalPatients 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.
Receives: Drug: dexamethasone; Drug: temsirolimus; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Course 1 (first 28 days)

  2. 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.

    Measured: Continuously from start of treatment study

Secondary outcomes (5)

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

    We will examine a scatter plot of the absolute and Percent change in PBMNC versus the absolute and percent change in BM. Spearman (non-parametric) and Pearson (parametric) correlation coefficients and linear and/or spline smoothing regression on either the original or a transformed scale will be used to assess the relationship. We will compare mean and median levels in those who respond versus those who do not using the Wilcoxon rank sum test and we will report the percent of overlap in P70 between the two groups. Assessed using analysis of variance methods or their non-parametric analog.

    Measured: Every 4 weeks

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

    Assessed by immunohistochemistry (IHC). We will first carry out a bivariate assessment of AKT percent positivity versus the binary outcome of response versus no response to treatment. For AKT score, we will compare mean and median levels in those who respond versus those who do not using the Wilcoxon rank sum test and we will report the percent of overlap in AKT between the two groups.

    Measured: Every 4 weeks

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

    PTEN expression will be determined by IHC. We will first carry out a bivariate assessment of PTEN score versus the binary outcome of response versus no response to treatment. For PTEN variables, we will report the corresponding contingency table versus response and use Wilcoxon test to assess the association if applicable.

    Measured: Every 4 weeks

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

    We will first carry out a bivariate assessment of RAS mutational status versus the binary outcome of response versus no response to treatment. For RAS variables, we will report the corresponding contingency table versus response and use Fishers exact test to assess the association.

    Measured: Every 4 weeks

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

    We will first carry out a bivariate assessment of MYC mutational status versus the binary outcome of response versus no response to treatment. For MYC variables, we will report the corresponding contingency table versus response and use Fishers exact test to assess the association.

    Measured: Every 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2008 (estimated)
  2. Study startDec 2008
  3. Primary completionAug 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00693433
Sponsor's protocol ID
NCI-2009-00157
Other IDs
VAMC-SC-7353, CDR0000597181
Status last verified
Jun 2013
First submitted
6 Jun 2008
Last updated
4 Dec 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing dexamethasone, temsirolimus and laboratory biomarker analysis in people with Refractory Multiple Myeloma and Stage I Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose of temsirolimus (time frame: Course 1 (first 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00693433.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2015.

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