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 2
  • Study Type

  • Status

  • Study Participants

RATIONALE: 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.


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.


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.
Study Started
Jun 10
Last Update
Jul 10

Drug arsenic trioxide

Drug ascorbic acid

Drug melphalan

Procedure chemosensitization/potentiation

Procedure chemotherapy



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



18 and over

Performance status

Karnofsky 60-100%

Life expectancy

More than 3 months


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


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


Calcium < 14 mg/dL


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


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


Biologic therapy

More than 4 weeks since prior immunotherapy or antibody therapy


See Disease Characteristics
More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

Endocrine therapy

See Disease Characteristics
No other concurrent corticosteroids


More than 4 weeks since prior radiotherapy


More than 4 weeks since prior major surgery


No other concurrent investigational agents
No Results Posted