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

Phase 3

Completed

• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Interventions: Drug: Thalidomide; Drug: zoledronic acid

• Registration Number: NCT00432458
• Lead Sponsor: Mayo Clinic

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.

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.

Study Timeline

• Study Start: 2003-07
• Study First Submitted: 2007-02-05
• Study First Submitted QC: 2007-02-05
• Study First Posted: 2007-02-07
• Primary Completion: 2011-06
• Study Completion: 2012-04
• Results First Submitted: 2012-04-11
• Status Verified: 2012-06
• Results First Submitted QC: 2012-06-04
• Last Update Submitted: 2012-06-04
• Results First Posted: 2012-07-04
• Last Update Posted: 2012-07-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I: Thal/ZLD	Thalidomide	Thalidomide (Thal) + Zolendronic acid (ZLD)
Arm I: Thal/ZLD	zoledronic acid	Thalidomide (Thal) + Zolendronic acid (ZLD)
Arm II: ZLD	zoledronic acid	Zoledronic acid (ZLD)

Primary Outcome Measures

Name	Time	Method
Time to Disease Progression (TTP)	randomization to progression (up to 5 years)	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.

Secondary Outcome Measures

Name	Time	Method
12-month Progression-free Survival (PFS)	12 months	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.
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	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
Duration of Response (Complete Response, Partial Response, and Very Good Partial Response)	time from start of response to progression (up to 5 years)	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
Time to Subsequent Treatment	time from end of treatment to subsequent treatment (up to 5 years)	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
Time to Treatment Failure	time from randomization to treatment failure (up to 5 years)	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
Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events	During treatment (up to 5 years)	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

Trial Locations

Locations (4)

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States

Mayo Clinic Scottsdale; 🇺🇸 Scottsdale, Arizona, United States

Mayo Clinic - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States