Phase II Study of ONTAK in Previously Treated Patients With Low-grade Non-Hodgkin's Lymphoma (NHL)

A Randomized, Multicenter, Phase II Evaluation of ONTAK (Denileukin Diftitox) in Patients With Previously Treated, Indolent, B-Cell, Non-Hodgkin's Lymphoma

The purpose of this study is to look at the safety and effectiveness of ONTAK in previously treated patients with NHL.

Inclusion Criteria:

• Pathological diagnosis of low-grade (indolent), B-cell, non-Hodgkin's lymphoma.

• Positive expression for CD25 of tumor cells in a lymph node biopsy as defined by greater than 20% of malignant cells staining for CD25 by standardized immunohistochemical assay.

• Modified Ann Arbor Stage I, II, III or IV.

• Patients must have received at least two but no more than five prior therapies. One prior therapy must have been cytotoxic chemotherapy and one prior therapy must have been monoclonal antibody therapy. Combination chemotherapy, including regimens used prior to bone marrow transplantation, will count as a single therapy for purposes of eligibility.

• Patients must have bidimensionally measurable disease.

• Patients must be 18 years of age or older.

• An ECOG performance status of 0, 1, or 2.

• Acceptable organ function defined as follows:

  • absolute neutrophil count (ANC) > or = to 1,000/mm3, platelet count > or = to 50,000/mm3, Hemoglobin > or = to 8 g/dL;
  • Bilirubin < or = to 1.5 times the upper limit of normal (ULN);
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < or = to 1.5 times the upper limit of normal;
  • Serum creatinine <1.8mg/dL;
  • Serum albumin > or = to 3.0 g/dL.

• New York Heart Association classification of I or II and no history of poorly controlled hypertension.

• Must be free of serious concurrent illness.

• Female patients must meet the following criteria:

  • If the patient is a female of childbearing potential, she must have negative serum beta human chorionic gonadotropin (B-hCG) pregnancy test within seven days prior to study entry and must have used an effective means of contraception or have been sexually abstinent for at least four weeks prior to the negative serum pregnancy test and through to study entry.
  • Female patients of childbearing potential must agree to practice an effective method of birth control during the entire treatment period and for at least three weeks after their last treatment on protocol.

Exclusion Criteria:

• Patients with cutaneous T-cell lymphoma.
• Patients previously treated with ONTAK (DAB389lL-2) or DAB486IL-2.
• Inability to comply with protocol requirements for this study.
• Pregnant women or lactating women who are breast feeding or women planning to become pregnant during the treatment period or three weeks after their last treatment on protocol.
• Serious intercurrent medical illnesses or active infections requiring parenteral antibiotics, which would interfere with the ability of the patient to carry out the treatment program.
• Sero-positive for human immunodeficiency virus (HIV) antibody. History of ongoing Hepatitis B or Hepatitis C infection.
• Another malignancy or history of another cancer with less than five disease-free years (other than resected basal or squamous cell skin cancers or in situ cervical cancer).
• Patients with a known hypersensitivity to ONTAK or any of its components: diphtheria toxin, interleukin-2, or excipients.
• Any investigational agents within one month prior to study entry.
• Prior radiation therapy within four weeks of enrollment or to the only site of evaluable disease.