A Phase III Randomized Trial of Thalidomide Plus Zoledronic Acid Versus Zoledronic Acid Alone in Patients With Early Stage Multiple Myeloma
- Compare time to progression in patients with early stage multiple myeloma treated with
zoledronate with or without thalidomide.
- 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.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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)
Thomas E. Witzig, MD
United States: Food and Drug Administration
|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|