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

NCT00006021 | Completed Phase 1 DMC

• 3 other identifiers: 20000156CDR0000068033SCCC-2000010
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course

Secondary Outcomes (1)

• Toxicity as measured by CTCAE criteria

Interventions

ascorbic acid DIETARY_SUPPLEMENT

arsenic trioxide DRUG

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Miami: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Cedars Medical Center

Miami, Florida, 33136, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Baptist-South Miami Regional Cancer Program

Miami, Florida, 33176-2197, United States

Location

Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Related 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 glutathione for the treatment of relapsed/refractory multiple myeloma. Clin Cancer Res. 2002 Dec;8(12):3658-68.

  PMID: 12473574 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Ascorbic Acid; Arsenic Trioxide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Officials

• Kelvin Lee, MD

  University of Miami Sylvester Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2000
• First Posted: January 27, 2003
• Study Start: June 1, 2000
• Primary Completion: May 1, 2006
• Study Completion: March 1, 2007
• Last Updated: December 15, 2016

Record last verified: 2016-12

Locations

US (4)