Title
Melphalan, Arsenic Trioxide, and Ascorbic Acid in Treating Patients With Relapsed or Refractory Multiple Myeloma
Phase II Study of Melphalan, Arsenic Trioxide, and Ascorbic Acid in Patients With Relapsed or Refractory Multiple Myeloma
Phase
Phase 2Lead Sponsor
OncotherapeuticsStudy Type
InterventionalStatus
WithdrawnIndication/Condition
Stage II Multiple Myeloma Stage III Multiple Myeloma Refractory Plasma Cell NeoplasmIntervention/Treatment
vitamin c arsenic trioxide melphalan ...Study Participants
0RATIONALE: Drugs used in chemotherapy, such as melphalan, arsenic trioxide, and ascorbic acid, work in different ways to stop cancer cells from dividing so they stop growing or die. Arsenic trioxide and ascorbic acid may also help melphalan kill more cancer cells by making them more sensitive to the drugs.
PURPOSE: This phase II trial is studying how well giving melphalan together with arsenic trioxide and ascorbic acid works in treating patients with relapsed or refractory multiple myeloma.
OBJECTIVES:
Primary
Determine the time to progression in patients with relapsed or refractory multiple myeloma (MM) treated with melphalan, arsenic trioxide, and ascorbic acid.
Determine the response rate (combined complete response, partial response, and minimal response) in patients treated with this regimen.
Determine the safety and tolerability of this regimen in these patients.
Secondary
Determine the time to response and overall survival of patients treated with this regimen.
Determine the effects of this regimen on renal failure associated with MM in these patients.
OUTLINE: This is an open-label, non-randomized, multicenter study.
Patients receive oral melphalan once daily on days 1-4 of week 1 and arsenic trioxide (ATO) IV over 1-2 hours and ascorbic acid IV over 15 minutes on days 1-4 of week 1 and then twice weekly during weeks 2-5. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression any time after course 1 also receive oral prednisone once daily on days 1-4 and 22-25 of each course. Patients achieving a complete response after 6 courses of therapy undergo bone marrow biopsy and receive no further therapy. Patients achieving stable disease or a partial response after 6 courses of therapy continue to receive ATO and ascorbic acid once weekly.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Diagnosis of multiple myeloma meeting at least 1 of the following criteria: Relapsed disease after a response to standard first-line chemotherapy (e.g., vincristine, doxorubicin, and dexamethasone [VAD] OR melphalan and prednisone) or first-line high-dose chemotherapy Refractory disease (failed to achieve at least stable disease) to most recent chemotherapy with or without systemic corticosteroids 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 No non-secretory myeloma No plasma cell leukemia PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy More than 3 months Hematopoietic Platelet count ≥ 50,000/mm^3 (30,000/mm^3 if bone marrow is extensively infiltrated) Hemoglobin ≥ 8.0 g/dL Absolute neutrophil count ≥ 1,000/mm^3 Pancytopenia secondary to multiple myeloma or hypersplenism allowed Hepatic AST and ALT ≤ 3 times upper limit of normal (ULN) Bilirubin ≤ 2 times ULN (unless clearly related to disease) No known active hepatitis B or C infection Renal Calcium < 14 mg/dL Cardiovascular No evidence of acute ischemia or new conduction system abnormality by electrocardiogram No myocardial infarction within the past 6 months No New York Heart Association class III or IV heart failure No poorly controlled hypertension No prolonged corrected QT interval (> 460 ms) with potassium > 4 mmol/L and magnesium ≥ 1.8 mmol/L Other No active infection No POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) No diabetes mellitus No other serious medical or psychiatric illness that would preclude study participation No known allergic reaction attributable to compounds of similar chemical or biological composition to study drugs No history of grand mal seizures HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior immunotherapy or antibody therapy Chemotherapy See Disease Characteristics More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) Endocrine therapy See Disease Characteristics No other concurrent corticosteroids Radiotherapy More than 4 weeks since prior radiotherapy Surgery More than 4 weeks since prior major surgery Other No other concurrent investigational agents
