Dexamethasone With or Without Oblimersen in Treating Patients With Relapsed or Refractory Multiple Myeloma

OBJECTIVES:

• Compare the time to disease progression in patients with relapsed or refractory multiple myeloma treated with dexamethasone with or without oblimersen.
• Compare the duration of response and objective response rate in patients treated with these regimens.
• Compare the proportion of patients without disease progression after 6 months and the proportion of patients who have not discontinued treatment after 6 months in these two patient groups.
• Compare the safety of these regimens in these patients.
• Compare survival of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to response to prior therapy (relapsed vs refractory), prior autologous stem cell transplantation (yes vs no), and number of prior therapy regimens (1-2 vs 3-6). Patients are randomized to 1 of 2 treatment arms.

Arm I

• Induction: Patients receive oblimersen (G3139) IV continuously on days 1-7 and 15-21 and oral dexamethasone daily on days 4-7, 11-14, and 18-21.
• Maintenance: One week after completion of induction therapy, patients with stable or responsive disease receive G3139 IV continuously on days 1-7 and oral dexamethasone daily on days 4-7. Courses repeat every 3 weeks for a maximum of 1 year in the absence of disease progression or unacceptable toxicity.

Arm II

• Induction: Patients receive oral dexamethasone daily for 4 days on weeks 1-3.
• Maintenance: One week after completion of induction therapy, patients with stable or responsive disease receive oral dexamethasone daily for 4 days. Courses repeat every 3 weeks for a maximum of 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years.

PROJECTED ACCRUAL: A total of 200 patients (100 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS: NOTE: This trial is being conducted at many institutions throughout the country. Please contact Genta for a site near you.

• Progressive multiple myeloma defined by one of the following:

• Primary resistance or progressive disease after achieving less than a partial response after at least 2 courses of combination chemotherapy (that included at least 1 myelosuppressive drug) within the past 3 months
• Relapsed or progressive disease after at least a partial response to prior therapy
• Progressive disease after high-dose chemotherapy and autologous stem cell transplantation
• Progressive disease defined by at least 1 of the following:

• Increase in serum M-protein by at least 50% or at least 2 g/dL above the lowest remission or baseline level
• Increase in urinary M-protein by at least 50% or at least 2 g/24 hours above lowest remission or baseline level
• Appearance of new lytic bone lesions or at least 50% increase in size of an existing bone lesion
• Quantifiable serum and/or urine paraprotein
• Bone marrow plasmacytosis at least 5% of total nucleated cells
• Measurable disease

• Serum M-protein level at least 1.0 g/dL OR
• Urinary M-protein excretion at least 200 mg/24 hours

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-3

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm3
• Platelet count at least 50,000/mm3
• No bleeding or coagulation disorder

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN
• PT and PTT no greater than 1.5 times ULN
• No history of chronic hepatitis or cirrhosis

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No active symptoms of coronary artery disease (e.g., uncontrolled arrhythmias or recurrent chest pain despite prophylactic medication)
• No New York Heart Association class III or IV heart disease
• No uncontrolled congestive heart failure
• No grade 2 or greater cardiovascular signs or symptoms within the past 4 weeks

Other:

• HIV negative
• No active peptic ulcer disease
• No uncontrolled seizure disorder
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No active uncontrolled infection
• No active autoimmune disease
• No hypersensitivity to phosphorothioate-containing oligonucleotides or to dexamethasone
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• At least 3 weeks since prior immunotherapy
• At least 72 hours since prior thalidomide
• Concurrent epoetin alfa allowed

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)

Endocrine therapy:

• At least 3 weeks since prior corticosteroids
• No concurrent chronic corticosteroids

Radiotherapy:

• At least 14 days since prior radiotherapy except limited radiotherapy to a single bone lesion

Surgery:

• At least 3 weeks since prior major surgery
• No prior organ allograft

Other:

• At least 4 weeks since other prior investigational therapy
• No more than 6 prior therapies for myeloma
• No concurrent immunosuppressive therapy