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

December 14, 2016 updated by: University of Miami

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center
      • Miami, Florida, United States, 33136
        • Cedars Medical Center
      • Miami, Florida, United States, 33176-2197
        • Baptist-South Miami Regional Cancer Program
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
Toxicity as measured by CTCAE criteria

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Miami

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Kelvin Lee, MD, University of Miami Sylvester Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2000

Primary Completion (ACTUAL)

May 1, 2006

Study Completion (ACTUAL)

March 1, 2007

Study Registration Dates

First Submitted

July 5, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

December 15, 2016

Last Update Submitted That Met QC Criteria

December 14, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20000156
  • CDR0000068033 (REGISTRY: PDQ (Physician Data Query))
  • SCCC-2000010 (OTHER: University of Miami Sylvester Comprehensive Cancer Center)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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