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

NCT00432458 | Completed Phase 3 Results DMC

• 4 other identifiers: CDR0000530050P30CA015083MC0289421-03
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage I multiple myeloma

Outcome Measures

Primary Outcomes (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.

  randomization to progression (up to 5 years)

Secondary Outcomes (6)

• 12-month Progression-free Survival (PFS)

  12 months

• 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

  12 months

• Duration of Response (Complete Response, Partial Response, and Very Good Partial Response)

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

• Time to Subsequent Treatment

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

• Time to Treatment Failure

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

Study Arms (2)

Arm I: Thal/ZLD

EXPERIMENTAL

Thalidomide (Thal) + Zolendronic acid (ZLD)

Drug: Thalidomide; Drug: zoledronic acid

Arm II: ZLD

EXPERIMENTAL

Zoledronic acid (ZLD)

Drug: zoledronic acid

Interventions

Thalidomide DRUG

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

Arm I: Thal/ZLD

zoledronic acid DRUG

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

Arm I: Thal/ZLD; Arm II: ZLD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 22902362 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Thalidomide; Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles; Azoles

Results Point of Contact

• Title: Dr. Thomas Witzig
• Organization: Mayo Clinic

witzig@mayo.edu

Study Officials

• Thomas E. Witzig, MD

  Mayo Clinic

  STUDY CHAIR

• Craig Reeder, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Vivek Roy, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2007
• First Posted: February 7, 2007
• Study Start: July 1, 2003
• Primary Completion: June 1, 2011
• Study Completion: April 1, 2012
• Last Updated: July 4, 2012
• Results First Posted: July 4, 2012

Record last verified: 2012-06

Locations

US (4)