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

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Completed

CT.gov ID

NCT00049374

Collaborator

National Cancer Institute (NCI) (NIH), University of Maryland Greenebaum Cancer Center (Other)

Locations

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: oblimersen sodium Drug: dexamethasone Drug: thalidomide	Phase 2

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2002

Actual Primary Completion Date :

Jan 1, 2006

Actual Study Completion Date :

Jan 1, 2006

Outcome Measures

Primary Outcome Measures

Complete and partial remission []

Secondary Outcome Measures

Relationship between molecular and clinical outcomes []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201-1592
2	St. Vincent's Comprehensive Cancer Center - Manhattan	New York	New York	United States	10011