RATIONALE: Biological therapies such as oblimersen may interfere with the growth of the cancer cells and slow or stop the growth of Waldenstrom's macroglobulinemia.

PURPOSE: Phase I/II trial to study the effectiveness of oblimersen in treating patients who have relapsed or refractory Waldenstrom's macroglobulinemia.

Condition	Treatment or Intervention	Phase
Waldenstrom's Macroglobulinemia	Drug: oblimersen  Procedure: antisense therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of oblimersen in patients with relapsed or refractory Waldenstrom's macroglobulinemia.
• Determine the response rate and duration of response in patients treated with this drug.
• Determine the safety of this drug in these patients.
• Determine the survival of patients treated with this drug.
• Determine the use of epoetin alfa in patients treated with this drug.
• Determine the clinical benefit of this drug, in terms of improvement in hemoglobin (greater than 11 g/dL) and platelet count (greater than 100,000/mm^3), in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

• Patients receive oblimersen IV continuously on days 1-7. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
• Phase II: Patients receive treatment as in phase I at the MTD of oblimersen. Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A maximum of 61 patients will be accrued for this study within approximately 3.2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of Waldenstrom's macroglobulinemia (WM) confirmed by both of the following:
• Bone marrow lymphoplasmacytosis with greater than 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy
• Measurable disease, defined by quantitative IgM monoclonal protein greater than 1,000 mg/dL
• Symptomatic relapsed or refractory disease requiring therapy, defined by at least 1 of the following:
• Impaired bone marrow function due to disease infiltration as demonstrated by any of the following:
• Hemoglobin less than 11 g/dL
• Requires epoetin alfa therapy to maintain hemoglobin of at least 11 g/dL
• Platelet count less than 100,000/mm^3
• Symptomatic bulky lymphadenopathy
• Symptoms attributable to hyperviscosity (e.g., nose bleeding, gingival bleeding, or retinal hemorrhage) or serum viscosity level relative to water greater than 4
• Received at least 1 prior chemotherapy regimen which included chlorambucil, cyclophosphamide, fludarabine, cladribine, or pentostatin
• No secondary leukemia or history of antecedent hematologic disorder (e.g., myelodysplasia) prior to initial onset of WM

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count at least 1,000/mm^3*
• Platelet count at least 50,000/mm^3*
• No bleeding disorder NOTE: *No requirement for transfusion or hematopoietic growth factor support

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST less than 1.5 times ULN
• Albumin at least 2.5 g/dL
• PT no greater than 1.5 times ULN OR
• INR no greater than 1.3
• PTT no greater than 1.5 times ULN
• No history of chronic hepatitis or cirrhosis

Renal

• Creatinine no greater than 2 times ULN

Cardiovascular

• No uncontrolled congestive heart failure
• No active symptoms of coronary artery disease, including the following:
• Uncontrolled arrhythmias
• Recurrent chest pain despite prophylactic medication
• No New York Heart Association class III or IV heart disease
• No grade 2 or greater cardiovascular signs and symptoms within the past 4 weeks

Immunologic

• HIV negative
• Direct Coombs' test negative
• No autoimmune thrombocytopenia
• No uncontrolled serious infection

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Adequate venous access for 7-day continuous infusion of study drug
• Intellectual, emotional, and physical ability to maintain an ambulatory infusion pump
• No other cancer except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other cancer from which the patient has been disease-free for at least 5 years
• No known hypersensitivity to phosphorothioate-containing oligonucleotides
• No uncontrolled seizure disorder

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 21 days since prior immunotherapy for WM
• More than 21 days since prior cytokine, biologic, or vaccine therapy for WM
• More than 8 weeks since prior plasmapheresis or plasma exchange
• No prior allogeneic stem cell transplantation
• No concurrent plasmapheresis or plasma exchange

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• No concurrent corticosteroid therapy

Radiotherapy

• More than 21 days since prior radiotherapy for WM

Surgery

• More than 21 days since prior major surgery for WM
• No prior organ allograft

Other

• Recovered from all prior therapy
• More than 21 days since other prior therapy for WM
• No other concurrent investigational therapy
• No concurrent immunosuppressive drugs
• No concurrent therapeutic anticoagulation therapy

Arizona
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States; Recruiting
District of Columbia
      Howard University Cancer Center at Howard University Hospital, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States; Recruiting
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201-1592,  United States; Recruiting
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-5256,  United States; Recruiting

Study chairs or principal investigators

Morie Abraham Gertz, MD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000304634; MAYO-MC0285; NCI-5826
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  June 5, 2003
ClinicalTrials.gov Identifier:  NCT00062244
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08