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Phase I/II Trial of Arsenic Trioxide (As2O3) With Ascorbic Acid in the Treatment of Relapsed/Refractory Multiple Myeloma

Phase 1/Phase 2
18 Years
Not Enrolling
Multiple Myeloma and Plasma Cell Neoplasm

Thank you

Trial Information

Phase I/II Trial of Arsenic Trioxide (As2O3) With Ascorbic Acid in the Treatment of Relapsed/Refractory Multiple Myeloma


- 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

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.

Inclusion Criteria


- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course

Safety Issue:


Principal Investigator

Kelvin Lee, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Miami Sylvester Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

June 2000

Completion Date:

March 2007

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • refractory multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



University of Miami Sylvester Comprehensive Cancer Center Miami, Florida  33136
Baptist-South Miami Regional Cancer Program Miami, Florida  33176
Cedars Medical Center Miami, Florida  33136
Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center Miami Beach, Florida  33140