RATIONALE: Thalidomide may slow the growth of cancer cells. Oblimersen may increase the effectiveness of thalidomide and dexamethasone by making cancer cells more sensitive to the drugs.

PURPOSE: Phase II trial to study the effectiveness of combining thalidomide and dexamethasone with oblimersen in treating patients who have relapsed or refractory multiple myeloma.

OBJECTIVES:

• Determine the clinical efficacy of oblimersen, thalidomide, and dexamethasone, in terms of complete and partial response rates, in patients with relapsed or refractory multiple myeloma.
• Determine the time to progression and duration of response in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Correlate disease response (clinical outcome) with changes in Bcl-2 levels in patients treated with this regimen.
• Determine the disease-free and overall survival of patients treated with this regimen.

OUTLINE: Patients receive induction therapy comprising oblimersen IV continuously on days 1-7, 22-28, and 43-49, oral dexamethasone on days 4-7, 25-28, and 46-49, and oral thalidomide daily beginning on day 4. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients with stable disease after induction therapy receive maintenance therapy comprising oblimersen IV continuously on days 1-7, oral dexamethasone on days 4-7, and oral thalidomide daily. Courses repeat every 35 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients are followed for 3 years.

PROJECTED ACCRUAL: A total of 10-46 patients will be accrued for this study within 10 months.

DISEASE CHARACTERISTICS:

• Histologically and clinically confirmed multiple myeloma

  • Relapsed and/or refractory after chemotherapy or transplantation

    • Patients with prior allogeneic transplantation must not have evidence of active graft-vs-host disease requiring immune suppression

• Measurable disease defined by quantitative immune globulin levels in serum and/or urine and bone marrow plasmacytosis

  • Patients with nonsecretory disease are eligible provided at least 1 plasmacytoma lesion is accurately measurable by MRI or CT scan
• No known CNS involvement

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count at least 1,000/mm^3*
• Platelet count at least 50,000/mm^3* NOTE: *Unless secondary to bone marrow plasmacytosis (more than 80% involvement)

Hepatic

• Bilirubin less than 2 times normal
• AST/ALT no greater than 3 times upper limit of normal

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Seizures allowed if under adequate control
• No severe skin reactions from prior thalidomide
• No prior allergic reactions attributed to agents used in this study
• No sensory or motor neuropathy grade II or greater
• No other uncontrolled concurrent illness that would preclude study therapy
• No ongoing or active infection
• No psychiatric illness or social situations that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 effective methods of contraception for 1 month before, during, and for 1 month after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• See Chemotherapy
• At least 6 weeks since prior thalidomide

Chemotherapy

• See Disease Characteristics
• No more than 4 prior chemotherapy regimens, including autologous and/or allogeneic stem cell transplantation regimens
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Concurrent continuous steroids allowed for chronic treatment of disorders other than myeloma

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior oblimersen
• No other concurrent anticancer therapies or investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients