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Arsenic Trioxide Plus Vitamin C in Treating Patients With Recurrent or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00006021
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : December 15, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Miami

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Vitamin C may increase the effectiveness of arsenic trioxide by making cancer cells more sensitive to the drug.

PURPOSE: Phase I/II trial to determine the effectiveness of arsenic trioxide plus vitamin C in treating patients who have recurrent or refractory multiple myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma and Plasma Cell Neoplasm Dietary Supplement: ascorbic acid Drug: arsenic trioxide Phase 1 Phase 2

Detailed Description:


  • Determine the maximum tolerated dose of arsenic trioxide when administered with ascorbic acid in patients with recurrent or refractory multiple myeloma.
  • Determine the therapeutic efficacy of this treatment combination in these patients.
  • Determine the expression of MDR and Bcl-xL genes and the intracellular levels of GSH in these patients before and after this treatment regimen and assess whether these measures have prognostic value.

OUTLINE: This is a multicenter, dose-escalation study of arsenic trioxide.

  • Phase I: Patients receive arsenic trioxide IV over 1-4 hours and ascorbic acid IV over 5-10 minutes on days 1-5 weekly for 5 weeks. Treatment continues every 7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive the MTD of arsenic trioxide with ascorbic acid as outlined above.

Patients are followed monthly for up to 5 years.

PROJECTED ACCRUAL: A total of 31-43 patients (6-18 for phase I and 16-25 for phase II) will be accrued for this study within 2.5 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Arsenic Trioxide (As2O3) With Ascorbic Acid in the Treatment of Relapsed/Refractory Multiple Myeloma
Study Start Date : June 2000
Actual Primary Completion Date : May 2006
Actual Study Completion Date : March 2007

Primary Outcome Measures :
  1. Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course

Secondary Outcome Measures :
  1. Toxicity as measured by CTCAE criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed multiple myeloma

    • M-protein by serum protein electrophoresis or urine protein electrophoresis
    • Quantitative determination of immunoglobulin
    • Bone marrow biopsy and aspirate with a plasma cell count greater than 10%
    • Refractory or chemoresistant disease defined as failure to respond (less than 50% reduction in M protein level) or progression within 2 months after receiving at least 2 chemotherapy regimens including:

      • Alkylating based regimen (melphalan) in combination with steroids (prednisone) or other chemotherapy regimens (e.g., vincristine, bleomycin, melphalan, cyclophosphamide, and prednisone or vincristine, carmustine, doxorubicin, and prednisone)
      • Vincristine, doxorubicin, and dexamethasone (VAD) regimen
      • Pulse therapy with high dose steroids alone
      • High dose alkylating agent and autologous stem cell transplantation
      • Allogeneic bone marrow transplantation
    • Plateau phase defined as M protein in the serum or urine for more than 6 weeks despite response to prior therapy

      • Must have received at least 2 of the chemotherapy regimens listed above or equivalent regimens
    • Recurrent disease defined as progression more than 2 months after initial therapy and failure to respond (less than 50% reduction or progression in M protein levels) to 1 chemotherapy regimen listed above or other salvage regimens (e.g., high-dose cyclophosphamide or topotecan)

      • Must have received VAD or other equivalent chemotherapy regimen
      • Should be considered for autologous or allogenic transplantation
      • Prior local radiotherapy allowed



  • Over 18

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified


  • WBC at least 2,000/mm^3*
  • Platelet count at least 50,000/mm^3* NOTE: *Unless attributable to bone marrow infiltration by multiple myeloma


  • Bilirubin less than 3 mg/dL
  • Transaminases less than 2.5 times upper limit of normal (ULN)


  • Creatinine less than 1.5 times ULN OR
  • Creatinine clearance at least 60 mL/min


  • No cardiac arrhythmias including recurrent supraventricular arrhythmia, any type of sustained ventricular arrhythmia, or conduction block (atrioventricular block grade II or III, left bundle branch block)
  • Ejection fraction at least 30%
  • No uncontrolled ischemic heart disease


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 4 months after study
  • HIV negative
  • No grade 3 or higher neurological disorder, including seizure disorders
  • No underlying medical condition that would preclude study
  • No other active malignancy except adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix


Biologic therapy:

  • See Disease Characteristics


  • See Disease Characteristics
  • At least 2 weeks since prior chemotherapy

Endocrine therapy:

  • See Disease Characteristics
  • Concurrent steroid treatment allowed except for primary treatment of myeloma


  • See Disease Characteristics
  • Concurrent local radiotherapy for pain or symptom control allowed provided the pain or symptom is not related to disease progression


  • Not specified


  • No other concurrent ascorbic acid supplements
  • No other concurrent investigational drug or therapy
  • Concurrent bisphosphonates allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00006021

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United States, Florida
Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
Cedars Medical Center
Miami, Florida, United States, 33136
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Baptist-South Miami Regional Cancer Program
Miami, Florida, United States, 33176-2197
Sponsors and Collaborators
University of Miami
National Cancer Institute (NCI)
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Study Chair: Kelvin Lee, MD University of Miami Sylvester Comprehensive Cancer Center

Publications of Results:
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Responsible Party: University of Miami Identifier: NCT00006021     History of Changes
Other Study ID Numbers: 20000156
CDR0000068033 ( Registry Identifier: PDQ (Physician Data Query) )
SCCC-2000010 ( Other Identifier: University of Miami Sylvester Comprehensive Cancer Center )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: December 15, 2016
Last Verified: December 2016

Keywords provided by University of Miami:
refractory multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Ascorbic Acid
Arsenic Trioxide
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Growth Substances
Antineoplastic Agents