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Multiple Myeloma and Plasma Cell NeoplasmPhase 3NCT00432458

Zoledronate With or Without Thalidomide in Treating Patients With Early Stage Multiple Myeloma

A Phase 3 study testing Thalidomide and zoledronic acid in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Mayo Clinic at 4 sites 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

RATIONALE: Zoledronate may prevent bone loss and stop the growth of cancer cells in bone. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. It is not yet know whether giving zoledronate together with thalidomide is more effective than zoledronate alone in treating multiple myeloma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Thalidomide and zoledronic acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
4 sitesUnited States
Study dates
Jul 2003to Apr 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma (MM)
  • Previously untreated asymptomatic disease
  • No requirement for immediate chemotherapy for active MM, such as hypercalcemia from myeloma or painful bone lesions
  • No solitary plasmacytoma
  • Measurable or evaluable disease as defined by one of the following:
  • Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
  • More than 200 mg of monoclonal protein in the urine by 24-hour electrophoresis
  • Measurable soft tissue plasmacytoma by physical exam with ruler or by MRI or positron emission tomography/CT scan
  • If the only measurable lesion is the plasmacytoma, it must be ≥ 1.5 cm in 1 dimension
  • Must have ≥ 10% plasma cells as measured on the bone marrow aspirate, bone marrow biopsy, or labeling index
  • No amyloidosis

PATIENT CHARACTERISTICS:

  • Performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8.0 g/dL
  • Creatinine ≤ 2.0 mg/dL (elevation above normal range should not be felt to be related to myeloma)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 methods of effective contraception 4 weeks before, during, and for 4 weeks after completion of study treatment
  • No uncontrolled infection
  • No other active malignancy
  • No New York Heart Association class III or IV heart disease
  • No pre-existing neuropathy ≥ grade 2
  • No concurrent major dental work

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior corticosteroids (for nonmalignant disorders) allowed
  • Prior therapy with experimental agents not shown to have significant activity in MM, such as clarithromycin, dehydroepiandrosterone, and anakinra allowed
  • No prior thalidomide or corticosteroids for MM
  • No more than 3 doses of IV zoledronate or pamidronate within the past 12 months
  • At least 3 months since prior radiotherapy, including radiotherapy for solitary plasmacytoma
  • No concurrent oral bisphosphonate therapy for osteoporosis

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona, 85259-5499

Other trials in United States

About this study

Official title: A Phase III Randomized Trial of Thalidomide Plus Zoledronic Acid Versus Zoledronic Acid Alone in Patients With Early Stage Multiple Myeloma

RATIONALE: Zoledronate may prevent bone loss and stop the growth of cancer cells in bone. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. It is not yet know whether giving zoledronate together with thalidomide is more effective than zoledronate alone in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying zoledronate and thalidomide see how well they work compared with zoledronate alone in treating patients with early stage multiple myeloma.

Read the detailed description

OBJECTIVES:

Primary

  • Compare time to progression in patients with early stage multiple myeloma treated with zoledronate with or without thalidomide.

Secondary

  • Compare the response rate, 1-year progression-free survival rate, duration of response, and time to next therapy in patients treated with these regimens.
  • Assess differences in toxicity of these regimens in these patients.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to the presence of lytic lesions on metastatic bone survey (yes vs no), beta-2 microglobulin level (high vs normal), and bone marrow labeling index (high [> 1.0%] vs low [≤ 1.0%]). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral thalidomide on days 1-28. Treatment with thalidomide repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive zoledronate IV over 15 minutes on day 1. Treatment with zoledronate repeats every 84 days for 1 year and once a year thereafter in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive zoledronate IV over 15 minutes on day 1. Treatment repeats every 84 days for 1 year and once a year thereafter in the absence of disease progression or unacceptable toxicity.

Blood samples are collected for research studies at baseline and after courses 3, 6, 9, and 12. Bone marrow aspirates are performed at baseline and after courses 6 and 12. Samples are evaluated for bone marrow angiogenesis; vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR-1), and VEGFR-2 expression; bone marrow angiogenesis-VEGF relationship; bone marrow angiogenesis/apoptosis rate relationship; bone marrow angiogenesis/plasma cell (PC) proliferation rate relationship; VEGF expression/apoptosis rate relationship; and VEGFR expression/PC proliferation rate relationship.

After completion of study treatment, patients are followed every 6 months for up to 5 years.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

Keywords
stage I multiple myeloma
Medical subject headings
Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

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

  • ThalidomideDrug

    200 mg orally on days 1-28 of 28 day cycle

  • zoledronic acidDrug

    4 mg^2 by IV on day 1 every 84 days for 1 year and once per year thereafter

Study groups in NCT00432458
Study groupRoleWhat they receive
Arm I: Thal/ZLDExperimentalThalidomide (Thal) + Zolendronic acid (ZLD)
Receives: Drug: Thalidomide; Drug: zoledronic acid
Arm II: ZLDExperimentalZoledronic acid (ZLD)
Receives: Drug: zoledronic acid

What is being measured

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

  1. Time to Disease Progression (TTP)

    Time to disease progression (TTP) was defined as the time from randomization to the earliest documentation of disease progression. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method, a two-sided (stratified) log-rank test was calculated.

    Measured: randomization to progression (up to 5 years)

Secondary outcomes (6)

  1. 12-month Progression-free Survival (PFS)

    PFS at 12 months is a dichotomized outcome indicating whether or not a participant was progression free (and alive) at 12 months from the date of randomization.

    Measured: 12 months

  2. Number of Participants With a Confirmed Response (Complete Response [CR], Very Good Partial Response [VGPR] or Partial Response [PR]) on Two Consecutive Evaluations at Least 2 Weeks Apart in the First 12 Months of Treatment

    Response is defined as follows:

    • CR: Complete disappearance of M-protein from serum \& urine on immunofixation, <5% plasma cells in bone marrow (BM)
    • VGPR: >=90% reduction in serum M-component; Urine M-Component <100 mg per 24 hours; <=5% plasma cells in BM
    • PR: >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels

    Measured: 12 months

  3. Duration of Response (Complete Response, Partial Response, and Very Good Partial Response)

    Duration of response (DOR) is defined as the time from first documentation of response (CR, VGPR or PR) to disease progression. The median DOR with 95% CI was estimated using the Kaplan Meier method

    Measured: time from start of response to progression (up to 5 years)

  4. Time to Subsequent Treatment

    Time to subsequent treatment (TTS) was defined as time from end of active (protocol) treatment to the start of subsequent treatment for participants with progressive disease. The median TTS with 95% CI was estimated using the Kaplan Meier method

    Measured: time from end of treatment to subsequent treatment (up to 5 years)

  5. Time to Treatment Failure

    Time to treatment failure (TTF) was defined as the time from randomization to the date at which the patient was removed from (protocol) treatment due to disease progression, unacceptable toxicity, participant refusal or death. The median TTF with 95% CI was estimated using the Kaplan Meier method

    Measured: time from randomization to treatment failure (up to 5 years)

  6. Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events

    Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 2.

    Description of Grades:

    Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death

    Measured: During treatment (up to 5 years)

Timeline

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

  1. First posted7 Feb 2007 (estimated)
  2. Study startJul 2003
  3. Primary completionJun 2011
  4. Study completionApr 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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00432458
Sponsor's protocol ID
CDR0000530050
Other IDs
P30CA015083, MC0289, 421-03
Status last verified
Jun 2012
First submitted
5 Feb 2007
Last updated
4 Jul 2012
Data monitoring committee
Yes

Publications

  • Witzig TE, Laumann KM, Lacy MQ, Hayman SR, Dispenzieri A, Kumar S, Reeder CB, Roy V, Lust JA, Gertz MA, Greipp PR, Hassoun H, Mandrekar SJ, Rajkumar SV. A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma. Leukemia. 2013 Jan;27(1):220-5. doi: 10.1038/leu.2012.236. Epub 2012 Aug 20.

    PubMed 22902362

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Thalidomide and zoledronic acid in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Mayo Clinic at 4 sites 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?

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 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Time to Disease Progression (TTP) (time frame: randomization to progression (up to 5 years)). 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 NCT00432458, which also lists 1 linked publication.

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 Jul 2012.

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