Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

Inclusion

Patients with CD20-expressing B cell NHL that is relapsed or refractory to standard therapy; CLL/SLL with peripheral blood leukemia/lymphoma cells and high-grade lymphomas (i.e., lymphoblastic lymphoma/Burkitt lymphoma) are excluded
Patients must have received prior Rituxan
Measurable disease; in the absence of lymphadenopathy, splenomegaly with defects or measurable extramedullary disease is acceptable; however, bone marrow involvement alone will not be included in the study
Age >=18 years and <=65 physiologic years of age
KPS >= 70%
Life expectancy >= 12 weeks
Serum creatinine =< 1.5 mg/dl
Total WBC >= 3000/ul or absolute neutrophil count (ANC) >= 1000/ul
Lymphocyte count >= 0.2 x 10^3/ul
Platelet count >= 75,000/ul
Hematocrit >= 25% or hemoglobin >= 9 g/100 ml
Alanine aminotransferase (ALT) =< 2.5 x UNL
Aspartate aminotransferase (AST) =< 2.5 x UNL
Total bilirubin (TBili) < 1.5 x UNL
Sodium, potassium, and phosphorus within normal limits
Chest x ray (CXR) within 4 weeks prior to Day 1 with no evidence of pulmonary congestion, pleural effusions, pulmonary fibrosis, or significant emphysema; if results are questionable, subjects would have additional lung function testing to exclude clinically relevant restriction or obstruction; subjects must have an FEV-1 and DLCO of at least 65% and 50% of expected, respectively
Electrocardiogram (12-lead ECG)
Echocardiogram (or MUGA) with normal left ventricular function
Cardiac stress test (e.g., stress thallium scan, stress echocardiography) with normal results if subject is suspected to have coronary artery disease
Fasting blood glucose (FBG) < 160 and hemoglobin (Hgb) A1C < 7% for subjects with diabetes mellitus (DM) or borderline DM
Women of procreative potential must have negative pregnancy test within the 2-week screening phase prior to Cycle 1, and all subjects of procreative potential must use adequate birth control throughout the study; subjects of procreative potential are defined as any fertile male, and any female who has experienced menarche and has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy) or is not post-menopausal, defined as age-related amenorrhea >= 12 months
Provide written informed consent prior to any screening procedures

Exclusion

Evidence of CNS lymphoma or lymphomatous meningitis
Prior treatment with IL-2
Type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusion of rituximab
Pregnant or lactating female
An immediate need for palliative radiotherapy or systemic corticosteroid therapy
Known intercurrent infections (including hepatitis C virus [HCV] and HIV or other conditions), or clinical evidence of these conditions
Actively infected with or chronic carriers of hepatitis B virus (HBV) as demonstrated by positive hepatitis B core antibody (HbcHb) or hepatitis B surface antigen (HbsAg); (subjects who are sero-positive only, i.e., surface antibody positive [HbsAg], are permitted)
Other significant active infection
Major surgery, chemotherapy, investigational agent, or radiation within 30 days of Day 1
Uncontrolled hypertension (diastolic >= 100 mmHg) or hypotension (systolic =< 90 mmHg)
History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmias
On ECG: a marked baseline prolongation of QT/QTc interval (> grade 2 QTc interval > 470 milliseconds)
History of medically significant ascites requiring repetitive paracentesis
Previous diagnosis of Addison's disease
Previous diagnosis of autoimmune disease (exceptions: subjects with autoimmune thyroiditis or vitiligo may be enrolled)
Organ transplant recipient
History of prior therapy or a serious, uncontrolled medical disorder that in the investigator's opinion would impair participation in the study
Known hypersensitivity to Tween-80 or human immunoglobulin
Legal incapacity or limited legal capacity
Patients with bulky lymph nodes (>= 10cm) or marked splenomegaly (i.e., extending into pelvis or crossing the midline)
Positive anti-DI-Leu16-IL2 antibody assay (where positive is defined as > 10% of the radiolabeled DI-Leu16-IL2 reactive with the subject's serum)