A Phase III Randomized Trial of Thalidomide Plus Zoledronic Acid Versus Zoledronic Acid Alone in Patients With Early Stage Multiple Myeloma
18 Years
N/A
Both
Multiple Myeloma and Plasma Cell Neoplasm
Trial Information
A Phase III Randomized Trial of Thalidomide Plus Zoledronic Acid Versus Zoledronic Acid Alone in Patients With Early Stage Multiple Myeloma
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Time to Disease Progression (TTP)
Outcome Description:
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.
Outcome Time Frame:
randomization to progression (up to 5 years)
Safety Issue:
No
Principal Investigator
Thomas E. Witzig, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000530050
NCT ID:
NCT00432458
Start Date:
July 2003
Completion Date:
April 2012
Related Keywords:
- Multiple Myeloma and Plasma Cell Neoplasm
- stage I multiple myeloma
- Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Mayo Clinic Scottsdale | Scottsdale, Arizona 85259 |
| Mayo Clinic - Jacksonville | Jacksonville, Florida 32224 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
