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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00006021
First received: July 5, 2000
Last updated: August 13, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Dietary Supplement: ascorbic acid
Drug: arsenic trioxide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:
  • Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity as measured by CTCAE criteria [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: June 2000
Study Completion Date: March 2007
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006021

Locations
United States, Florida
Baptist-South Miami Regional Cancer Program
Miami, Florida, United States, 33176-2197
Cedars Medical Center
Miami, Florida, United States, 33136
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
Sponsors and Collaborators
University of Miami Sylvester Comprehensive Cancer Center
Investigators
Study Chair: Kelvin Lee, MD University of Miami Sylvester Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00006021     History of Changes
Other Study ID Numbers: UMIAMI-20000156, CDR0000068033, SCCC-2000010, NCI-43
Study First Received: July 5, 2000
Last Updated: August 13, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:
refractory multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Ascorbic Acid
Arsenic trioxide
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 20, 2014