denileukin diftitox in treating patients with relapsed or refractory non-hodgkin's lymphoma

Conditions: Lymphoma

Summary: rationale: biological therapies, such as denileukin diftitox, may be able to carry cancer-killing substances directly to non-hodgkin's lymphoma cells. purpose: this phase ii trial is studying how well denileukin diftitox works in treating patients with relapsed or refractory b-cell non-hodgkin's lymphoma.

objectives: primary * determine the efficacy of denileukin diftitox, in terms of objective response and time to progression, in patients with relapsed or refractory b-cell non-hodgkin's lymphoma. secondary * determine the safety of this drug in these patients. * determine the 1-year overall survival of patients treated with this drug. outline: this is an open-label, multicenter study. patients receive denileukin diftitox iv over 20-80 minutes on days 1-3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, and 99 (weeks 1-16) in the absence of disease progression or unacceptable toxicity. patients achieving a partial response at week 16 may continue treatment once monthly for up to 8 additional doses or until a complete response (cr) is achieved. patients achieving a cr (at any time) receive 2 additional monthly doses of denileukin diftitox beyond cr. after completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter. projected accrual: a total of 25-50 patients will be accrued for this study within 1 year.

Eligibility criteria:
disease characteristics: * histologically confirmed b-cell non-hodgkin's lymphoma (nhl) of 1 of the following subtypes: * diffuse large b-cell lymphoma * follicular lymphoma (grades 1-3) * small lymphocytic lymphoma * transformed b-cell lymphoma * relapsed or refractory disease * disease failed to respond to or progressed after ≥ 2 prior treatment regimens (e.g., high-dose therapy \[hdt\] with stem cell transplantation \[sct\]\*) note: \*patients who have received hdt with sct are considered to have diminished bone marrow reserve * diminished bone marrow reserve and/or mild to moderate cytopenia, meeting 1 of the following criteria: * absolute neutrophil count ≥ 1,000/mm\^3 but \< 1,500/mm\^3 (growth factor independent) * wbc ≥ 2,000/mm\^3 but \< 4,000/mm\^3 (growth factor independent) * platelet count ≥ 40,000/mm\^3 (25,000/mm\^3 if thrombocytopenia is secondary to marrow involvement by lymphoma) but \< 150,000/mm\^3 (platelet transfusion independent) * at least 1 bidimensionally measurable lymph node or tumor mass ≥ 4 cm patient characteristics: age * 18 and over performance status * ecog 0-2 life expectancy * at least 16 weeks hematopoietic * see disease characteristics hepatic * bilirubin ≤ 1.5 times upper limit of normal (uln) * ast and alt ≤ 2 times uln * albumin ≥ 3.0 g/dl * no history of veno-occlusive disease of the liver * no chronic hepatitis renal * creatinine \< 2 times uln cardiovascular * no congestive heart failure * no new york heart association class iii-iv cardiac disease * no ventricular tachycardia * no fibrillation * no myocardial infarction within the past 12 months other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no known hiv positivity * no active gvhd ≥ grade 2 within the past 6 months * no other serious medical illness or active infection that would preclude study participation * no known hypersensitivity to denileukin diftitox or any of its components (e.g., diphtheria toxin, interleukin-2, or their excipients) * no other malignancy within the past 5 years except successfully treated carcinoma in situ of the cervix or basal cell carcinoma prior concurrent therapy: biologic therapy * see disease characteristics * at least 6 months since prior allogeneic sct * no concurrent immunotherapy chemotherapy * no concurrent chemotherapy endocrine therapy * no concurrent anticancer hormonal therapy * no concurrent corticosteroids for the treatment of nhl * concurrent corticosteroids allowed for the following conditions: * tapering doses of corticosteroids for resolving graft-versus-host disease (gvhd) * low-dose maintenance corticosteroids for the treatment of an autoimmune disorder * corticosteroids as premedication prior to denileukin diftitox administration or as transient treatment for hypersensitivity reactions radiotherapy * more than 4 weeks since prior and no concurrent radiotherapy * no prior radiotherapy to the only site of evaluable disease unless disease progression has occurred at that site surgery * not specified other * at least 3 weeks since prior antilymphoma therapy * more than 4 weeks since prior and no other concurrent experimental therapy, including approved drugs tested in an investigational setting

Keywords: recurrent adult diffuse large cell lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent small lymphocytic lymphoma