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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

Tracking Information
First Submitted Date  ICMJE July 5, 2000
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date December 15, 2016
Study Start Date  ICMJE June 2000
Actual Primary Completion Date May 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2007)
Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00006021 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2007)
Toxicity as measured by CTCAE criteria
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Arsenic Trioxide Plus Vitamin C in Treating Patients With Recurrent or Refractory Multiple Myeloma
Official Title  ICMJE Phase I/II Trial of Arsenic Trioxide (As2O3) With Ascorbic Acid in the Treatment of Relapsed/Refractory Multiple Myeloma
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma and Plasma Cell Neoplasm
Intervention  ICMJE
  • Dietary Supplement: ascorbic acid
  • Drug: arsenic trioxide
Study Arms  ICMJE Not Provided
Publications * Bahlis NJ, McCafferty-Grad J, Jordan-McMurry I, Neil J, Reis I, Kharfan-Dabaja M, Eckman J, Goodman M, Fernandez HF, Boise LH, Lee KP. Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin Cancer Res. 2002 Dec;8(12):3658-68.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 10, 2013)
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE March 2007
Actual Primary Completion Date May 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00006021
Other Study ID Numbers  ICMJE 20000156
CDR0000068033 ( Registry Identifier: PDQ (Physician Data Query) )
SCCC-2000010 ( Other Identifier: University of Miami Sylvester Comprehensive Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Miami
Study Sponsor  ICMJE University of Miami
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Kelvin Lee, MD University of Miami Sylvester Comprehensive Cancer Center
PRS Account University of Miami
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP