Arsenic Trioxide, Thalidomide, Dexamethasone, and Ascorbic Acid in Treating Patients With Relapsed or Refractory Multiple Myeloma

A Phase II Study of Arsenic Trioxide in Combination With Thalidomide, Dexamethasone, and Ascorbic Acid

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, dexamethasone, and ascorbic acid, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Sometimes when chemotherapy is given, it does not stop the growth of cancer cells. The cancer is said to be resistant to chemotherapy. Giving arsenic trioxide together with chemotherapy may reduce drug resistance and allow the cancer cells to be killed. Thalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Giving arsenic trioxide together with thalidomide, dexamethasone, and ascorbic acid may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with thalidomide, dexamethasone, and ascorbic acid works in treating patients with relapsed or refractory multiple myeloma.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Drug: arsenic trioxide; Drug: dexamethasone; Drug: thalidomide; Dietary supplement: ascorbic acid

Detailed Description

OBJECTIVES:

• Determine the safety and side effects of arsenic trioxide administered in combination with thalidomide, dexamethasone, and ascorbic acid in patients with relapsed or refractory multiple myeloma.
• Determine, preliminarily, the anticancer effects of this regimen in these patients.
• Determine the duration of anticancer effects in patients treated with this regimen.
• Determine the effect of this regimen on bone and immune function in these patients.

OUTLINE: Patients receive arsenic trioxide IV continuously and oral ascorbic acid once daily on days 1-5 in week 1 and twice weekly in weeks 2-12 and oral thalidomide once daily in weeks 1-14. Treatment with arsenic trioxide, ascorbic acid, and thalidomide repeats every 14 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral dexamethasone once daily on days 1-4. Treatment with dexamethasone repeats every 28 days.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma (MM)

  • Relapsed or refractory disease
• Monoclonal immunoglobulin spike by serum electrophoresis of ≥ 1 gm/dL AND/OR urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours
• Has received ≥ 2 prior treatment regimens for MM

• None of the following are allowed:

  • Non-secretory MM
  • Plasma cell leukemia
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Platelet count ≥ 50,000/mm^3 (30,000/mm^3 if the bone marrow is extensively infiltrated)
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count ≥ 1,000/mm^3

Hepatic

• AST and ALT < 3.0 times upper limit of normal (ULN)
• Bilirubin < 2.0 times ULN

Renal

• Not specified

Cardiovascular

• No cardiac disease, including any of the following conditions:

  • History of recurrent supraventricular arrhythmia
  • History of sustained ventricular tachycardia
  • History of second or third degree AV block
  • History of left bundle branch block
  • Cardiomyopathy with LVEF < 40%
  • Uncontrolled ischemic heart disease
• No myocardial infarction within the past 6 months
• No prolonged QT interval > 500 ms

Other

• Not pregnant or nursing
• Negative pregnancy test
• No HIV positivity
• No neuropathy > grade 3
• Potassium ≥ 4 mEq/L
• Magnesium ≥ 1.8 mg/dL

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 30 days since prior investigational drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arsenic Trioxide; Arsenic Trioxide in Combination With Thalidomide, Dexamethasone, and Ascorbic Acid	Drug: arsenic trioxide; Drug: dexamethasone; Drug: thalidomide; Dietary supplement: ascorbic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate (complete response, partial response, and minimal response) as measured by bone marrow aspirate, biopsy, cytogenetic analysis, serum, urine, and immunofixation skeletal survey at 6 months and end of study treatment

Secondary Outcome Measures

Outcome Measure
Safety and tolerability as measured by physical exams, blood tests, and adverse events reports weekly

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Aleksandra Simic, MD, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): February 1, 2006
• Study Completion (Actual): February 1, 2006

Study Registration Dates

• First Submitted: September 26, 2005
• First Submitted That Met QC Criteria: September 26, 2005
• First Posted (Estimate): September 28, 2005

Study Record Updates

• Last Update Posted (Estimate): May 28, 2012
• Last Update Submitted That Met QC Criteria: May 24, 2012
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: refractory multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Anti-Bacterial Agents; Leprostatic Agents; Vitamins; Antioxidants; Dexamethasone; Thalidomide; Arsenic Trioxide; Ascorbic Acid
• Other Study ID Numbers: CDR0000443708; P30CA069533 (U.S. NIH Grant/Contract); OHSU-1277 (Other Identifier: OHSU IRB); OHSU-HEM-03100-L (Other Identifier: OHSU Knight Cancer Institute)