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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of dexamethasone by making cancer cells more sensitive to the drug. It is not yet known if dexamethasone is more effective with or without oblimersen in treating multiple myeloma. PURPOSE: Randomized phase III trial to compare the effectiveness of dexamethasone with or without oblimersen in treating patients who have relapsed or refractory multiple myeloma.

Detailed Description
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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.

Official Title
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Randomized Phase III Study of Dexamethasone With or Without Genasense (Bcl-2 Antisense Oligonucleotide) in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: oblimersen sodium
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: oblimersen sodium|nan|
|Drug: dexamethasone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma