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

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006021
• Other study ID #: 20000156
• Secondary ID: CDR0000068033SCC
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 5, 2000
• Last updated: December 14, 2016
• Start date: June 2000
• Est. completion date: March 2007

Study information

• Verified date: December 2016
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: March 2007
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Dietary Supplement:
• ascorbic acid

Drug:
• arsenic trioxide

Locations

Country	Name	City	State
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	Cedars Medical Center	Miami	Florida
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center	Miami Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 glutathio — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course			No
Secondary	Toxicity as measured by CTCAE criteria			Yes