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

NCT ID: NCT00006021

Last Updated: 2016-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-06-30
• Study Completion Date: 2007-03-31

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

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

refractory multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

ascorbic acid

Intervention Type: DIETARY_SUPPLEMENT

arsenic trioxide

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kelvin Lee, MD

Role: STUDY_CHAIR

University of Miami Sylvester Comprehensive Cancer Center

Locations

Cedars Medical Center

Miami, Florida, United States

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Baptist-South Miami Regional Cancer Program

Miami, Florida, United States

Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center

Miami Beach, Florida, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 12473574 (View on PubMed)

Other Identifiers

CDR0000068033

Identifier Type: REGISTRY

Identifier Source: secondary_id

SCCC-2000010

Identifier Type: OTHER

Identifier Source: secondary_id

20000156

Identifier Type: -

Identifier Source: org_study_id