Oblimersen, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase II Study Of Genasense In Combination With Thalidomide And Dexamethasone In Relapsed And Refractory Multiple Myeloma

Conditions
-----------------
Multiple Myeloma and Plasma Cell Neoplasm

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete and partial remission |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between molecular and clinical outcomes |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
refractory multiple myeloma