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

Last updated: December 14, 2016
Sponsor: University of Miami
Overall Status: Completed

Phase

1/2

Condition

Leukemia

Lymphoproliferative Disorders

Multiple Myeloma

Treatment

N/A

Clinical Study ID

NCT00006021
20000156
SCCC-2000010
CDR0000068033
  • Ages 18-120
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • Over 18

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • 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

Hepatic:

  • Bilirubin less than 3 mg/dL

  • Transaminases less than 2.5 times upper limit of normal (ULN)

Renal:

  • Creatinine less than 1.5 times ULN OR

  • Creatinine clearance at least 60 mL/min

Cardiovascular:

  • 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

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics

Chemotherapy:

  • 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

Radiotherapy:

  • See Disease Characteristics

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

Surgery:

  • Not specified

Other:

  • No other concurrent ascorbic acid supplements

  • No other concurrent investigational drug or therapy

  • Concurrent bisphosphonates allowed

Study Design

Total Participants: 22
Study Start date:
June 01, 2000
Estimated Completion Date:
March 31, 2007

Study Description

OBJECTIVES:

  • 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.

Connect with a study center

  • Baptist-South Miami Regional Cancer Program

    Miami, Florida 33176-2197
    United States

    Site Not Available

  • Cedars Medical Center

    Miami, Florida 33136
    United States

    Site Not Available

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida 33136
    United States

    Site Not Available

  • Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center

    Miami Beach, Florida 33140
    United States

    Site Not Available

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