Arsenic Trioxide, Thalidomide, Dexamethasone, and Ascorbic Acid in Treating Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, dexamethasone, and ascorbic acid, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Sometimes when chemotherapy is given, it does not stop the growth of cancer cells. The cancer is said to be resistant to chemotherapy. Giving arsenic trioxide together with chemotherapy may reduce drug resistance and allow the cancer cells to be killed. Thalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Giving arsenic trioxide together with thalidomide, dexamethasone, and ascorbic acid may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with thalidomide, dexamethasone, and ascorbic acid works in treating patients with relapsed or refractory multiple myeloma.

Detailed Description
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OBJECTIVES: Determine the safety and side effects of arsenic trioxide administered in combination with thalidomide, dexamethasone, and ascorbic acid in patients with relapsed or refractory multiple myeloma. Determine, preliminarily, the anticancer effects of this regimen in these patients. Determine the duration of anticancer effects in patients treated with this regimen. Determine the effect of this regimen on bone and immune function in these patients. OUTLINE: Patients receive arsenic trioxide IV continuously and oral ascorbic acid once daily on days 1-5 in week 1 and twice weekly in weeks 2-12 and oral thalidomide once daily in weeks 1-14. Treatment with arsenic trioxide, ascorbic acid, and thalidomide repeats every 14 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral dexamethasone once daily on days 1-4. Treatment with dexamethasone repeats every 28 days. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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A Phase II Study of Arsenic Trioxide in Combination With Thalidomide, Dexamethasone, and Ascorbic Acid

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Dietary Supplement: ascorbic acid
* Drug: arsenic trioxide
* Drug: dexamethasone
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of multiple myeloma (MM) Relapsed or refractory disease Monoclonal immunoglobulin spike by serum electrophoresis of ≥ 1 gm/dL AND/OR urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours Has received ≥ 2 prior treatment regimens for MM None of the following are allowed: Non-secretory MM Plasma cell leukemia Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome PATIENT CHARACTERISTICS: Age Over 18 Performance status ECOG 0-2 Life expectancy More than 3 months Hematopoietic Platelet count ≥ 50,000/mm^3 (30,000/mm^3 if the bone marrow is extensively infiltrated) Hemoglobin ≥ 8.0 g/dL Absolute neutrophil count ≥ 1,000/mm^3 Hepatic AST and ALT < 3.0 times upper limit of normal (ULN) Bilirubin < 2.0 times ULN Renal Not specified Cardiovascular No cardiac disease, including any of the following conditions: History of recurrent supraventricular arrhythmia History of sustained ventricular tachycardia History of second or third degree AV block History of left bundle branch block Cardiomyopathy with LVEF < 40% Uncontrolled ischemic heart disease No myocardial infarction within the past 6 months No prolonged QT interval > 500 ms Other Not pregnant or nursing Negative pregnancy test No HIV positivity No neuropathy > grade 3 Potassium ≥ 4 mEq/L Magnesium ≥ 1.8 mg/dL PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other More than 30 days since prior investigational drugs

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: Arsenic Trioxide<br>Arsenic Trioxide in Combination With Thalidomide, Dexamethasone, and Ascorbic Acid | Dietary Supplement: ascorbic acid<br> <br> Drug: arsenic trioxide<br> <br> Drug: dexamethasone<br> <br> Drug: thalidomide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete response, partial response, and minimal response) as measured by bone marrow aspirate, biopsy, cytogenetic analysis, serum, urine, and immunofixation skeletal survey at 6 months and end of study treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as measured by physical exams, blood tests, and adverse events reports weekly |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory multiple myeloma