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Refractory Multiple MyelomaPhase 1NCT00310024

Vorinostat and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

A Phase 1 study testing bortezomib, vorinostat 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 vorinostat when given together with bortezomib in treating patients with relapsed or refractory multiple myeloma. Vorinostat and bortezomib 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?
bortezomib, vorinostat and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
Nov 2005to Feb 2008
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

  • Histologically and clinically confirmed multiple myeloma
  • Relapsed or refractory disease after prior chemotherapy or transplantation*
  • Measurable disease, defined by quantitative immunoglobulin levels in serum and/or urine and bone marrow plasmacytosis
  • Non-secretory disease allowed provided MRI or positron emission tomography or CT scan can accurately measure at least one plasmacytoma lesion
  • No known CNS involvement
  • Life expectancy > 3 months
Show all 33Show fewer
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Absolute neutrophil count ≥ 1,000/mm³ (unless myelosuppression is secondary to bone marrow plasmacytosis [> 80% involvement])
  • Platelet count ≥ 50,000/mm³ (unless myelosuppression is secondary to bone marrow plasmacytosis [> 80% involvement])
  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • AST and ALT ≤ 2 times ULN
  • Creatinine < 2 mg/dL OR creatinine clearance > 40 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to swallow pills
  • Patients with a history of seizures are eligible provided seizures are under adequate control with non-enzyme inducing anticonvulsant medication
  • No history of allergic reactions attributed to study agents
  • No sensory or motor neuropathy ≥ grade II
  • No uncontrolled current illness including, but not limited to, the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit study compliance
  • No grade 3 QT prolongation (i.e., > 500 msec) at baseline
  • See Disease Characteristics
  • Prior bortezomib allowed
  • At least 2 weeks since prior therapy for multiple myeloma
  • Concurrent growth factors (filgrastim [G-CSF] and epoetin alfa) to sustain peripheral blood counts (during the first course of therapy only) allowed
  • Concurrent steroid therapy (≤ 20 mg of prednisone) for patients requiring chronic use for disorders other than myeloma allowed
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational or commercial agents or therapies for this malignancy

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201-1595

Other trials in United States

About this study

Official title: A Phase I Study of SAHA in Combination With Bortezomib in Relapsed and Refractory Multiple Myeloma

This phase I trial is studying the side effects and best dose of vorinostat when given together with bortezomib in treating patients with relapsed or refractory multiple myeloma. Vorinostat and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with bortezomib may kill more cancer cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose (MTD) of vorinostat (SAHA) when given together with bortezomib in patients with relapsed or refractory multiple myeloma (MM).

II. Determine the toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

  1. Determine whether giving SAHA together with bortezomib inhibits histone deacetylation in normal cells (buccal mucosal cells and/or peripheral blood monocytes) as well as in MM cells.

II. Evaluate the effect of dexamethasone when given together with SAHA and bortezomib.

III. Explore molecular mechanisms involved in apoptosis in MM mediated by SAHA and bortezomib.

IV. Correlate change of histone acetylation with clinical outcome in patients treated with this regimen.

OUTLINE: This is a multicenter, dose escalation study of vorinostat (SAHA).

Patients receive bortezomib IV on days 1, 4, 8, and 11 followed by oral SAHA twice daily on days 4-11. Beginning in course 3, some patients may receive low-dose oral dexamethasone on days 4-8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional cohort of 10 patients receive treatment at the MTD.

Patients undergo blood collection and tumor biopsies periodically during study for pharmacologic and biomarker correlative studies.

After completion of study treatment, patients are followed at least once a month.

Being tested
bortezomib, vorinostat, laboratory biomarker analysis, pharmacological study
Medical subject headings
Multiple Myeloma

What participants receive

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

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV

  • vorinostatDrug

    Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

    Given orally

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00310024
Study groupRoleWhat they receive
Treatment (vorinostat, bortezomib)ExperimentalPatients receive bortezomib IV on days 1, 4, 8, and 11 followed by oral SAHA twice daily on days 4-11. Beginning in course 3, some patients may receive low-dose oral dexamethasone on days 4-8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional cohort of 10 patients receive treatment at the MTD. Patients undergo blood collection and tumor biopsies periodically during study for pharmacologic and biomarker correlative studies.
Receives: Drug: bortezomib; Drug: vorinostat; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

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

  1. Maximum tolerated dose (MTD) of SAHA in combination with bortezomib determined by dose-limiting toxicities

    Measured: 21 days

Secondary outcomes (3)

  1. Inhibition of histone deacetylation

    Measured: Up to 1 month

  2. Response

    The estimates and the corresponding 90% confidence intervals will be calculated.

    Measured: Up to 1 month

  3. Survival (disease specific and overall)

    Will be estimated using the Kaplan-Meir method.

    Measured: Up to 1 month

Timeline

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

  1. First posted3 Apr 2006 (estimated)
  2. Study startNov 2005
  3. Primary completionFeb 2008

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
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00310024
Sponsor's protocol ID
NCI-2012-02693
Other IDs
GCC 0514, N01CM62204, CDR0000466109
Status last verified
Feb 2013
First submitted
29 Mar 2006
Last updated
7 Feb 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bortezomib, vorinostat 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 33 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 7 Feb 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 SAHA in combination with bortezomib determined by dose-limiting toxicities (time frame: 21 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 NCT00310024.

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 7 Feb 2013.

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