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

NeuroTherapia, Inc.

Status and phase

Withdrawn

Phase 2

Conditions

Refractory Plasma Cell Neoplasm

Stage III Multiple Myeloma

Stage I Multiple Myeloma

Stage II Multiple Myeloma

Treatments

Procedure: antiangiogenesis therapy

Procedure: chemotherapy

Procedure: biological therapy

Drug: dexamethasone

Procedure: growth factor antagonist therapy

Drug: ascorbic acid

Drug: thalidomide

Procedure: anti-cytokine therapy

Procedure: non-specific immune-modulator therapy

Drug: arsenic trioxide

Procedure: drug resistance inhibition

Study type

Interventional

Funder types

Other

Identifiers

NCT00112879

CDR0000428248 (Registry Identifier)

CCF-IRB-7469

CCF-CTI-T12016

CCF-IRB-5241

Details and patient eligibility

About

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. Thalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Giving arsenic trioxide together with ascorbic acid, dexamethasone, and thalidomide may kill more cancer cells.

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

Full description

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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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