Bortezomib, Ascorbic Acid, and Melphalan in Treating Patients With Newly Diagnosed Multiple Myeloma

Study Overview
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Brief Summary
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RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Ascorbic acid may help melphalan work better by making cancer cells more sensitive to the drug. Giving bortezomib together with ascorbic acid and melphalan may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with ascorbic acid and melphalan works in treating patients with newly diagnosed multiple myeloma.

Detailed Description
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OBJECTIVES: Primary Determine the overall response rate (combined complete response [CR], near CR, partial response [PR], and minimal response [MR]) and time to progression of disease in patients with newly diagnosed multiple myeloma treated with bortezomib, ascorbic acid, and melphalan. Assess the safety and tolerability of this regimen in these patients. Secondary Assess the time to response in these patients. Determine progression-free and overall survival of these patients. Assess time to disease progression among subjects who continue to maintenance treatment with bortezomib. OUTLINE: This is an open-label study. Induction therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral melphalan and oral ascorbic acid on days 1-4. Treatment repeats every 28 days to maximum response [MR] or for at least 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease receive an additional 2 courses of induction therapy beyond MR and proceed to maintenance therapy. Patients with stable disease or without a maximum reduction in their paraprotein after 8 courses of induction therapy are eligible to receive maintenance therapy. Maintenance therapy: Patients receive bortezomib IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Official Title
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A Phase II Trial of Bortezomib + Ascorbic Acid + Melphalan (BAM) Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Dietary Supplement: ascorbic acid
* Drug: bortezomib
* Drug: melphalan


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Newly diagnosed symptomatic multiple myeloma based on the following criteria: Durie-Salmon staging Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours Symptomatic disease No POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes) No plasma cell leukemia PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Life expectancy > 3 months Platelet count ≥ 50,000/mm³ (30,000/mm³ if the bone marrow is extensively infiltrated) Hemoglobin ≥ 8.0 g/dL Absolute neutrophil count ≥ 1,000/mm³ Creatinine ≤ 3 mg/dL Sodium > 130 mmol/L corrected AST and ALT ≤ 3 times upper limit of normal (ULN) Bilirubin ≤ 2 times ULN unless clearly related to the disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Any ECG abnormality has to be documented by the investigator as not medically relevant No electrocardiographic evidence of acute ischemia or new conduction system abnormalities No myocardial infarction or EKG evidence of infarction within the past 6 months No active infection No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL [3.5 mmol/L]) No New York Heart Association class III or IV heart failure No uncontrolled angina No severe uncontrolled ventricular arrhythmias No active conduction system abnormalities No poorly controlled hypertension No diabetes mellitus No known HIV infection No known active hepatitis B or C viral infection No history of grand mal seizures No history of allergic reaction to compounds of similar chemical or biological composition to melphalan, bortezomib, boron, or mannitol No peripheral neuropathy ≥ grade 2 within the past 14 days No other serious medical or psychiatric illness that could potentially interfere with the completion of study treatment PRIOR CONCURRENT THERAPY: More than 4 weeks since prior immunotherapy, antibody therapy, or radiotherapy More than 4 weeks since prior major surgery No prior therapy for myeloma Prior prednisone at a total of 400mg over ≤ 4 days (or an equivalent potency of another steroid) allowed No concurrent corticosteroids (≥ 10 mg prednisone/day or equivalent) No other concurrent investigational agents No other concurrent antimyeloma therapy

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: ascorbic acid|nan|
|Drug: bortezomib|nan|
|Drug: melphalan|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (complete response [CR], near CR, partial response, and minimal response) |  |  | 
| Safety and tolerability as assessed by NCI CTCAE v3.0 |  |  | 
| Proportion of patients responding |  |  | 
| Time to disease progressionin patients receiving maintenance treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to response |  |  | 
| Progression-free survival |  |  | 
| Overall survival as assessed by the Kaplan-Meier method |  |  | 
| Time to disease progression |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma