NCT00258245

Arsenic Trioxide and Ascorbic Acid Combined With Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma or Plasma Cell Leukemia

A Phase I Study of Arsenic Trioxide and Ascorbic Acid (ATO/AA) in Combination With Low Dose Velcade-Thalidomide-Dexamethasone (VTD) in Relapsed/Refractory Multiple Myeloma (MM)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Barbara Ann Karmanos Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Ascorbic acid may help arsenic trioxide work better by making cancer cells more sensitive to the drug. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Giving arsenic trioxide and ascorbic acid together with bortezomib, thalidomide, and dexamethasone may stop the growth of and kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with ascorbic acid, bortezomib, thalidomide, and dexamethasone in treating patients with relapsed or refractory multiple myeloma or plasma cell leukemia.

Detailed description

OBJECTIVES: Primary * Determine the dose-limiting toxicity of arsenic trioxide when given in combination with ascorbic acid, bortezomib, thalidomide, and dexamethasone, particularly in terms of sensory neuropathy, in patients with relapsed or refractory multiple myeloma or plasma cell leukemia. Secondary * Determine the overall response rate, complete response rate, and response duration in patients treated with the maximum tolerated dose of this regimen. * Determine whether the addition of arsenic trioxide and ascorbic acid to the treatment regimen (beginning in course 2) increases NFKB inhibition in these patients during courses 2 and 3 compared to course 1. OUTLINE: This is a multicenter, dose-escalation study of arsenic trioxide. * Induction therapy: Patients receive bortezomib IV over 3-5 seconds and dexamethasone IV or orally on days 1, 4, 8, and 11 and oral thalidomide once daily on days 1-21 (course 1). For course 2 and all subsequent courses, patients receive arsenic trioxide IV over 1-2 hours, ascorbic acid IV over 15 minutes, bortezomib IV over 3-5 seconds, and dexamethasone IV or orally on days 1, 4, 8, and 11 and thalidomide once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a plateau in response proceed to maintenance therapy. * Maintenance therapy: Patients receive oral dexamethasone every other day and oral thalidomide once daily 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 determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Conditions

• Multiple Myeloma and Plasma Cell Neoplasm

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	ascorbic acid	Ascorbic Acid (Vit C)- 1000 mg IVPB after Arsenic Trioxide \[ATO\] days 1, 4, 8, 11
DRUG	arsenic trioxide	Arsenic Trioxide (Trisenox)- 0.10→0.15→0.25 mg/kg/dose IVPB days 1, 4, 8, 11
DRUG	bortezomib	Bortezomib (Velcade)- 0.7→1.0 mg/m2 IVP days 1, 4, 8, 11
DRUG	dexamethasone	Dexamethasone (Decadron)- 40 mg/days IVPB or PO d 1, 4, 8, 11
DRUG	thalidomide	Thalidomide (Thalomid) - 50 mg/day by mouth (PO)
DRUG	Aspirin	Aspirin - 325 mg by mouth (PO) every day

Timeline

• Start date: 2005-05-01
• Primary completion: 2008-04-01
• Completion: 2008-04-01
• First posted: 2005-11-24
• Last updated: 2013-04-29

Locations

1 site across 1 country: United States