Clinical trial NCT00227682: Arsenic Trioxide, Thalidomide, Dexamethasone, and Ascorbic Acid in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official title: A Phase II Study of Arsenic Trioxide in Combination With Thalidomide, Dexamethasone, and Ascorbic Acid
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: refractory multiple myeloma
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-09-28
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
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 outcomes:
measure: Safety and tolerability as measured by physical exams, blood tests, and adverse events reports weekly
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Aleksandra Simic, MD
role: PRINCIPAL_INVESTIGATOR
References: