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Refractory Multiple MyelomaPhase 1NCT00398515

Lenalidomide and Temsirolimus in Treating Patients With Previously Treated Multiple Myeloma

A Phase 1 study testing lenalidomide, temsirolimus and pharmacological study in people with Refractory Multiple Myeloma and Stage II 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 lenalidomide in treating patients with previously treated multiple myeloma. Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
lenalidomide, temsirolimus and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
Mar 2007to Feb 2012
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

  • 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
Show all 55Show fewer
  • 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
  • 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 years
  • 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 [GM-CSF])
  • No concurrent grapefruit or grapefruit juice

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose of CCI-779 (temsirolimus) when given together with lenalidomide in patients with previously treated multiple myeloma.

SECONDARY OBJECTIVES:

  1. 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.

Being tested
lenalidomide, temsirolimus, pharmacological study, 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.

  • lenalidomideDrug

    Also called CC-5013, IMiD-1, Revlimid

    Given orally

  • temsirolimusDrug

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

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00398515
Study groupRoleWhat they receive
Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)ExperimentalPatients 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.
Receives: Drug: lenalidomide; Drug: temsirolimus; Other: pharmacological study; 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 (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.

    Measured: Course 1 (first 28 days)

Secondary outcomes (5)

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

    Measured by NCI CTCAE version 3.0.

    Measured: From the time of their first treatment with lenalidomide and temsirolimus

  2. Pharmacokinetic analysis of lenalidomide

    Plasma drug levels will be measured by liquid chromatography and tandem mass spectroscopy.

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

  3. Pharmacodynamics of temsirolimus in peripheral blood mononuclear cells (PBMC)

    PBMC will be used to assess the phosphorylation status of p70S6K to evaluate the pharmacodynamic activity of each dose level. This will assist in determining the biologically active dose in the event that dose limiting toxicity is not observed. The analysis of p70^S6K and phospho (P)-p70^S6K will be assessed by Western blotting using specific antibodies. The expression level will be quantified by densitometry. The inhibition of P- p70S6K will be correlated with clinical endpoints and PK parameters.

    Measured: Days 1 and 8 of course 1

  4. 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

    Assessed by ELISA.

    Measured: Baseline and then every 4 weeks

  5. Assessment of peripheral blood immune cell subsets

    We will investigate immune cell subsets by flow-cytometry.

    Measured: Baseline and then 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 posted10 Nov 2006 (estimated)
  2. Study startMar 2007
  3. Primary completionFeb 2012

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
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00398515
Sponsor's protocol ID
NCI-2009-00151
Other IDs
NCI-2009-00151, OSU-2006C0040, CDR0000514831, OSU-05115, 05115, 7314, U01CA076576
Status last verified
Sep 2013
First submitted
9 Nov 2006
Last updated
30 Sep 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing lenalidomide, temsirolimus and pharmacological study in people with Refractory Multiple Myeloma and Stage II 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 55 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 30 Sep 2013. 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 (MTD) of temsirolimus when given together with lenalidomide (time frame: Course 1 (first 28 days)). 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 NCT00398515.

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 30 Sep 2013.

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