Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

• Status: Terminated
• Trial end date: 2012-10-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Oblimersen sodium may help chemotherapy work better by making cancer cells more sensitive to the drugs. Giving oblimersen sodium together with combination chemotherapy may kill more cancer cells. PURPOSE: This clinical trial is studying the side effects of giving oblimersen sodium together with combination chemotherapy and to see how well it works in treating patients with newly diagnosed stage I, stage II, stage III, or stage IV diffuse large B-cell lymphoma

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Nebraska
• Collaborators: Genta Incorporated; National Cancer Institute (NCI)
• Treatments: Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Oblimersen; Prednisone; Rituximab; Vincristine

Criteria

Inclusion Criteria:

• Newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) (any stage) OR composite lymphoma with >= 50% DLBCL

• Adequate diagnostic tissue for microarray gene expression analysis or IHC analysis

• Karnofsky Performance Status >= 70 (ECOG 0, 1)

• No prior chemotherapy (with the exception of 1 cycle CHOP-R based on current diagnosis, clinical condition, and availability/feasibility of initiating Genasense), immunotherapy, radiotherapy, or investigational therapies for NHL; steroid therapy is allowed only if required for maintenance of another chronic disease (e.g., rheumatoid arthritis)

• Patients aged >= 60 years, or patients with a history of coronary artery disease, congestive heart failure, hypertension, diabetes, or hyperlipidemia must have an estimated ejection fraction >= 0.45 (45%) by MUGA or echocardiography, performed within two months of study entry

• Patients must be willing to give written informed consent, and sign an institutionally approved consent form prior to initiating genasense or any study related activities (i.e., Genasense & microarray)

• Females of childbearing potential must have a negative serum pregnancy test prior to enrollment in the study

• Adequate venous access for 7-day continuous infusion

• Patients without evidence of severe organ dysfunction as determined within two weeks of 1st cycle of CHOP-R: 1) Hemoglobin > 8 g/dl; 2) Absolute neutrophil count > 1000/; 3) Platelets > 100,000 (lower blood counts may be acceptable if due to lymphoma after review with principal investigator); 4) Creatinine =< 2.0 mg/dL (unless due to NHL); 5) Bilirubin =< 2.0 mg/dL; 6) AST =< 3 x upper normal; 7) ALP =< 3 x upper normal (unless due to NHL)

• Men and women of reproductive potential must agree to use TWO of the following forms of birth control every time they have sex throughout the study and for up to 3 months following discontinuation of study drug: hormonal birth control methods, condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicidal, IUD, or surgical sterilization while participating in this study

Exclusion Criteria:

• Significant medical disease other than cancer including: 1) Any bleeding or coagulation disorder including a history of autoimmune hemolytic anemia or autoimmune thrombocytopenia; 2) Severe pulmonary disease; 3) Uncontrolled congestive heart failure; 4) New York Heart Association class III or IV disease; 5) Uncontrolled seizure disorder; and 6) Active infections

• Less than 3 weeks from prior major surgery

• Prior organ allograft

• Known HIV infection (due to expected frequent occurrence of myelo-suppression and immunosuppression)

• Women who are pregnant (confirmed by a serum pregnancy test in females of reproductive potential) or breast-feeding (women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment or remain abstinent)

• Women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment (unless the subject or subject's partner(s) is sterile, i.e., women who have had a hysterectomy or have been post-menopausal for at least twelve consecutive months) or remain abstinent

• Known hypersensitivity to phosphorothiate-containing oligonucleotides

• Concurrent investigational, corticosteroid therapy or any other anti-cancer treatments (such as chemotherapy, radiation, biologic or investigational therapies) while receiving protocol therapy; other than one cycle CHOP-R allowed based on current diagnosis, clinical condition, and availability/feasibility of initiating Genasense; other than chronic steroid use for another indication (For stage I/II or as clinically indicated- involved field irradiation as per standard practice is accepted)

• Other investigational drug therapy within 30 days of study entry

• Secondary leukemia or history of antecedent hematologic disorder

• History of second cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for three or more years)

• No active CNS disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma

• Concomitant anticoagulant therapy is not permitted (with the exception of 1 mg/day of warfarin for central line prophylaxis)

• Known hypersensitivity to G3139 (Genasense) or R-CHOP

• Neurologic disorders, overt psychosis, mental disability or evidence of limited capacity to provide fully informed consent or cooperation with the complexities of the treatment program