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

Sponsors and Collaborators:	OHSU Knight Cancer Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00227682

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Dietary Supplement: ascorbic acid Drug: arsenic trioxide Drug: dexamethasone Drug: thalidomide	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study of Arsenic Trioxide in Combination With Thalidomide, Dexamethasone, and Ascorbic Acid

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Arsenic Cancer Multiple Myeloma

Drug Information available for: Dexamethasone Thalidomide Ascorbic acid Dexamethasone acetate Doxiproct plus Arsenic trioxide Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety and tolerability as measured by physical exams, blood tests, and adverse events reports weekly [ Designated as safety issue: Yes ]

Study Start Date:

June 2004

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.

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00227682

Locations

United States, Oregon
Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239-3098

Sponsors and Collaborators

OHSU Knight Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Aleksandra Simic, MD

OHSU Knight Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000443708, OHSU-8203, OHSU-1277, OHSU-HEM-03100-L
Study First Received:	September 26, 2005
Last Updated:	April 4, 2009
ClinicalTrials.gov Identifier:	NCT00227682 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

refractory multiple myeloma

Study placed in the following topic categories:

Anti-Inflammatory Agents
Dexamethasone
Anti-Infective Agents
Antioxidants
Immunologic Factors
Thalidomide
Blood Protein Disorders
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Paraproteinemias
Hemostatic Disorders
Hormones
Anti-Bacterial Agents
Hemorrhagic Disorders

Vitamins
Micronutrients
Dexamethasone acetate
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Hematologic Diseases
Blood Coagulation Disorders
Vascular Diseases
Arsenic trioxide
Trace Elements
Angiogenesis Inhibitors
Immunosuppressive Agents
Glucocorticoids
Multiple Myeloma
Vitamin C

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Dexamethasone
Anti-Infective Agents
Antioxidants
Immunologic Factors
Thalidomide
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Paraproteinemias
Hemostatic Disorders
Hormones

Anti-Bacterial Agents
Hemorrhagic Disorders
Therapeutic Uses
Vitamins
Cardiovascular Diseases
Growth Inhibitors
Angiogenesis Modulating Agents
Micronutrients
Dexamethasone acetate
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Growth Substances

ClinicalTrials.gov processed this record on September 11, 2009