Combination Bisphosphonate and Anti-Angiogenesis Therapy With Pamidronate and Thalidomide

Study Overview
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Brief Summary
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The purpose of this research is to study how helpful the combination of thalidomide and Pamidronate or thalidomide and Zometa is in controlling the myeloma disease and to study any side effects.

Detailed Description
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Recently laboratory research found that thalidomide can inhibit the formation of new blood vessels that are necessary for the growth and spread of cancer. In order to grow and increase in size tumors require new blood vessels to supply them with the necessary blood to grow. If we can prevent these new blood vessels feeding the tumor from being formed by using thalidomide we might slow or stop the growth of the tumor. This concept is called anti-angiogenesis It is hoped that thalidomide will slow or stop the growth myeloma. However, it cannot be guaranteed that you will benefit if you take part in this study. The treatment you receive may even be harmful.

Official Title
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UARK 98-036, A Phase II Trial of Combination Bisphosphonate and Anti-Angiogenesis Therapy With Pamidronate and Thalidomide in Patients With Smoldering/Indolent Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Pamidronate
* Drug: Thalidomide
* Drug: Zometa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a diagnosis of Smoldering or Indolent myeloma All patients must be informed of the investigational nature of this study and must sign a written informed consent in accordance with UAMS Human Research Advisory Committee and federal guidelines. Exclusion Criteria: Prior bisphosphonate therapy within 30 days prior to study entry. Serum creatinine > 5 mg/dl, ascites, or serum direct bilirubin > 2.5 mg/dl. Prior plicamycin or calcitonin within 2 weeks of study entry. Severe cardiac disease, unstable thyroid disease, or epilepsy. Prior radiation therapy to > 20% of the skeleton.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thalidomide + Bisphosphonate<br>200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy | Drug: Pamidronate<br>* Patients will receive either pamidronate or zometa. Pamidronate is administered at a dose of 90 mg by continuous infusion over 90 minutes, every two weeks for 2 months. Disease will be reassessed after two cycles. Those with stable disease or better will receive 90 mg every 4 weeks as maintenance therapy.<br>Drug: Thalidomide<br>* All Patients will receive thalidomide 200 mg as an oral, once daily dose. Dose may be reduced to as low as 50 mg qod in the event of severe toxicity. Thalidomide will continue daily as tolerated until criteria to remove from study are met. Patients will receive appropriate regimen to prevent constipation (i.e., colace, dulcolax, milk of magnesia, or lactulose)<br>Drug: Zometa<br>* Patients will receive either pamidronate or zometa. Zometa is administered at a dose of 4 mg by continuous infusion every two weeks for 2 months. Disease will be reassessed after two cycles. Those with stable disease or better will receive 4 mg every 4 weeks as maintenance therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response | Best response to study treatment as defined by protocol-specific response criteria: Complete Response (CR) = absence of urine and serum M-components by immunofixation; bone marrow should be adequately cellular (>20%) with <1% monoclonal plasma cells by DNA-clg flow cytometry; serum calcium level must be normal; no new bone lesions nor enlargement of existing lesions; Normalization of serum concentrations of normal immunoglobulins is not required for CR. Partial Response (PR) = Reduction by > 75% in serum myeloma protein production; Decrease in monoclonal marrow plasmacytosis to <5%; Decrease in Bence-Jones proteinuria by >90%; No new lytic bone lesions or soft tissue plasmacytoma. Treatment Failures/Progressive Disease (PD) = Such patients do not fulfill the above criteria and/or have new lytic lesions (but not compression fractures), hypercalcemia, or other new manifestations of disease. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloma, Thalidomide, Pamidronate, Aredia, Bisphosphonate, Anti-Angiogenesis, Smoldering/Indolent Myeloma, Zometa