Higher Frequency Zoledronic Acid in the Treatment of Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether lower than conventional doses of dexamethasone and thalidomide; and a higher dosing frequency of zoledronic acid are effective in the treatment of newly-diagnosed multiple myeloma.

Detailed Description
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Patients with newly-diagnosed multiple myeloma (MM) may be treated using monthly cycles of dexamethasone plus thalidomide (DT). Unfortunately, the use of conventional doses of DT is associated with significant treatment-related morbidity and mortality, which is comparable to that observed with conventional chemotherapy. Hence, for safety reasons, patients frequently receive lower than conventional doses of DT (i.e. dt), and potentially experience a poorer anti-MM effect. The highly-potent aminobisphosphonate, zoledronic acid (Z), has been shown in pre-clinical mouse models to exhibit an impressive anti-MM effect. It is therefore possible to combined dt with Z (i.e. dtZ) to enhance the efficacy of (lower dose) dt. In addition, the anti-tumor effect of dtZ may potentially be augmented by using Z at a higher (three-weekly) dosing frequency.

Official Title
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An International, Multicenter, Non-Randomized, Open-Labeled Study to Evaluate the Efficacy of Lower Dose Dexamethasone/Thalidomide and Higher Frequency ZOMETA(TM) in the Treatment of Previously Untreated Patients With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: dexamethasone
* Drug: thalidomide
* Drug: zoledronic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at or above 21 years Clinical diagnosis of MM Active MM with measurable disease Signed written informed consent Signed consent for drug safety program for thalidomide Exclusion Criteria: Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS) Patients with Indolent MM (IMM), or Smouldering MM (SMM) Known hypersensitivity (including severe cutaneous reactions) to d, t or Z Fulminant sepsis Females in the reproductive age group who refuse contraception Pregnancy 24 hr urinary creatinine clearance time (CCT) <30 ml/min Previous renal transplantation Severe peripheral neuropathy Recurrent DVT or PE Severe arrhythmias and cardiac conduction disorders Liver dysfunction of active viral hepatitis Osteonecrosis of the jaws (ONJ)

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dtZ regimen, Initial therapy<br>To test the efficacy of the dtZ regimen in previously untreated patients with multiple myeloma. | Drug: dexamethasone<br>* 20 mg, PO (orally) on days 1-4, 8-11 and 15-18 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops.<br>* Other names: DEXAMETHASONE BEACONS;Drug: thalidomide<br>* 100 mg, PO (orally) on days 1-21 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops.<br>* Other names: THADO (TTY);Drug: zoledronic acid<br>* 4 mg, IV (in the vein) on day 1 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops.<br>* Other names: ZOMETA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. To determine response rates (RR) and disease progression rates in all MM patients treated with dtZ regimen. |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess overall survival (OS) in all patients treated with dtZ regimen. |  | 4 months | 
| Assessment of incidence of skeletal related events (SREs). |  | 4 months | 
| Assessment of percent change in renal function in all patients. |  | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Steroids, Fluorinated, Thalidomide, Bisphosphonates