Oblimersen in Treating Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia
Waldenström Macroglobulinemia
About this trial
This is an interventional treatment trial for Waldenström Macroglobulinemia
Eligibility Criteria
Inclusion Criteria: 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 Performance status - ECOG 0-2 Not specified See Disease Characteristics Absolute neutrophil count at least 1,000/mm^3* Platelet count at least 50,000/mm^3* No bleeding disorder 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 INR no greater than 1.3 PTT no greater than 1.5 times ULN No history of chronic hepatitis or cirrhosis Creatinine no greater than 2 times ULN 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 HIV negative Direct Coombs' test negative No autoimmune thrombocytopenia No uncontrolled serious infection 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 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 See Disease Characteristics No concurrent corticosteroid therapy More than 21 days since prior radiotherapy for WM More than 21 days since prior major surgery for WM No prior organ allograft 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
Sites / Locations
- Mayo Clinic in Arizona
- Howard University Hospital
- Mayo Clinic in Florida
- University of Maryland Greenebaum Cancer Center
- Johns Hopkins University
- Barbara Ann Karmanos Cancer Institute
- Mayo Clinic
- University of Wisconsin Hospital and Clinics
Arms of the Study
Arm 1
Experimental
Arm I
Phase I: 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.