Phase II Study of Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Patients With Previously Untreated High-Risk or Relapsed or Refractory Multiple Myeloma
18 Years
N/A
Both
Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma, Refractory Plasma Cell Neoplasm
Trial Information
Phase II Study of Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Patients With Previously Untreated High-Risk or Relapsed or Refractory Multiple Myeloma
OBJECTIVES:
Primary
- Determine the response rate in patients with previously untreated high-risk or relapsed
or refractory multiple myeloma (MM) treated with arsenic trioxide, ascorbic acid,
dexamethasone, and thalidomide.
- Determine the safety of this regimen in these patients.
Secondary
- Determine the duration of response, progression-free survival, and overall survival of
patients with previously untreated high-risk MM treated with this regimen.
OUTLINE: This is an open-label study.
- Induction therapy: Patients receive arsenic trioxide IV over 1-4 hours and ascorbic
acid IV over 15-30 minutes on days 1-5 in week 1 and then twice weekly in weeks 2-12;
oral dexamethasone on days 1-4, 11-14, 29-32, 39-42, 57-60, and 67-70 (weeks 1, 2, 5,
6, 9, and 10); and oral thalidomide once daily in weeks 1-12.
- Consolidation therapy: Beginning 4 weeks after completion of induction therapy,
patients receive arsenic trioxide and ascorbic acid as in induction therapy; oral
dexamethasone on days 1-4, 29-32, and 57-60 (weeks 1, 5, and 9); and oral thalidomide
once daily in weeks 1-12.
- Maintenance therapy: Beginning 4 weeks after completion of consolidation therapy,
patients receive arsenic trioxide IV over 1-4 hours and ascorbic acid IV over 15-30
minutes on days 1, 8, 15, and 22. Treatment with arsenic trioxide and ascorbic acid
repeats every 90 days (every 12 weeks). Patients also receive oral dexamethasone on
days 1-4. Treatment with dexamethasone repeats every 28 days. Patients receive oral
thalidomide once daily. Maintenance therapy continues in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 4 weeks and then every 6
months thereafter.
PROJECTED ACCRUAL: A total of 33-68 patients (15-34 with previously untreated high-risk
multiple myeloma [MM] and 18-34 with relapsed or refractory MM) will be accrued for this
study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of multiple myeloma (MM), meeting 1 of the following criteria:
- Previously untreated disease with poor prognosis, meeting 1 of the following
criteria:
- Active disease with β2 microglobulin ≥ 5.5 mg/dL
- Inactive disease with peripheral plasma cells OR chromosome 13 or 14 abnormalities by
fluorescent in situ hybridization
- Relapsed or refractory disease
- Measurable disease by serum and urine M-protein and/or measurable plasmacytoma
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2* NOTE: *ECOG 3 allowed for patients with bone pain due to MM
Life expectancy
- At least 3 months
Hematopoietic
- Platelet count ≥ 75,000/mm^3 unless plasma cells > 50% in bone marrow
- Any WBC allowed provided plasma cells > 50% in bone marrow
Hepatic
- SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)
- Bilirubin ≤ 2.5 times ULN
Renal
- Creatinine ≤ 6.0 mg/dL
Cardiovascular
- Absolute QT interval ≤ 460 msec with potassium ≥ 4.0 mEq/L AND magnesium ≥ 1.8 mg/dL
- No conduction defects
- No unstable angina
- No myocardial infarction within the past 6 months
- No congestive heart failure
- No New York Heart Association class II-IV heart disease
- No other significant underlying cardiac dysfunction
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception for ≥ 4 weeks before,
during, and for ≥ 4 weeks after completion of study therapy
- No blood, ova, or sperm donation during study participation
- No history of grand mal seizures except infantile febrile seizures
- No pre-existing neurotoxicity or neuropathy ≥ grade 2
- No uncontrolled diabetes mellitus
- No active serious infection that cannot be controlled with antibiotics
- No other malignancy within the past 5 years except curatively treated carcinoma in
situ of the cervix or nonmelanoma skin cancer
- No other condition that would preclude study compliance or follow up
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Prior thalidomide allowed (in patients with relapsed or refractory MM)
- No prior thalidomide in combination with arsenic trioxide
- Prior epoetin alfa allowed
Chemotherapy
- See Biologic therapy
- Prior arsenic trioxide allowed (for patients with relapsed or refractory MM)
- No concurrent cytotoxic chemotherapy
- No chemotherapy within 2 weeks after completion of study treatment
Endocrine therapy
- Prior steroid therapy allowed (for patients with relapsed or refractory MM)
Radiotherapy
- No concurrent broad-field radiotherapy
Surgery
- Not specified
Other
- Prior and concurrent bisphosphonates allowed
- No other concurrent investigational agents
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Mohamad A. Hussein, MD
Investigator Role:
Study Chair
Investigator Affiliation:
The Cleveland Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000428248
NCT ID:
NCT00112879
Start Date:
Completion Date:
Related Keywords:
- Stage I Multiple Myeloma
- Stage II Multiple Myeloma
- Stage III Multiple Myeloma
- Refractory Plasma Cell Neoplasm
- Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
Name | Location |
|---|---|
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
