A Study of ONTAK in Patients With Relapsed or Refractory, B-Cell Non Hodgkin's Lymphoma
A Study of ONTAK in Patients With Relapsed or Refractory, B-Cell Non Hodgkin's Lymphoma
The goal of this clinical research study is to find out if the study drug, ONTAK (denileukin
 diftitox), can shrink or slow the growth of B-cell non-Hodgkin's lymphoma (NHL) in patients
 whose disease has not responded to prior treatments, or has relapsed after an initial
 response to prior treatments. The safety of treatment with ONTAK will also be studied. The
 hypothesis is that patients with relapsed or refractory B-cell NHL and mild to moderate
 myelosuppression treated with ONTAK at a new dosing regimen will respond sufficiently to
 warrant further study.
Inclusion Criteria:

 -  Relapsed or refractory B-Cell NHL

 -  Histological documentation of diffuse large B-cell lymphoma, follicular lymphoma
 (grade 1, 2, or 3), small lymphocytic lymphoma or transformed B-Cell lymphoma.

 -  Bi-dimensionally measurable disease with at least one lymph node or tumor mass
 measuring > or equal to 4 cm2

 -  ECOG performance status less than or equal to 2.

 -  Failure to respond or progression of disease after 2 or more prior treatment regimens;
 this may include high dose therapy (HDT) with stem cell transplantation (SCT).
 Patients with prior HDT plus SCT will be considered as having "diminished bone marrow
 reserve"

 -  At least 18 years of age

 -  At least 3 weeks from last anti-lymphoma therapy

 -  Mild to moderate cytopenia defined as any of the following:

 -  ANC > or equal to 1,000/microL and < 1,500/microL off growth factors

 -  WBC counts > or equal to 2,000/microL and < 4,000/microL off growth factors or

 -  Platelet count > or equal to 40,000/microL (25,000/microL if thrombocytopenia is
 secondary to marrow involvement by lymphoma) and < 150,000/microL.

 -  Acceptable organ function defined as all of the following:

 -  Bilirubin < or equal to 1.5 times the upper limit of normal (ULN)

 -  SGOT (AST) and SGPT (ALT) < or equal to 2 times the ULN.

 -  Serum creatinine < 2 times ULN.

 -  Serum albumin > or equal to 3.0 g/dL

 -  Female patient of childbearing potential must have a negative pregnancy test within
 seven days prior to study drug administration, and must agree to use an effective
 means of contraception throughout the study.

 -  Life expectancy of at least 16 weeks.

 -  Patients must have reviewed, signed and dated a witnessed informed consent document
 that has been approved by the IRB of each participating center.

 Exclusion Criteria:

 -  Less than 6 months from prior allogeneic stem cell transplant and/or patient with
 active graft versus host disease (GVHD) Grade > or equal to 2.

 -  Prior history of veno-occlusive disease of the liver.

 -  Inability to comply with protocol requirements of this study for intravenous
 administration of ONTAK.

 -  Pregnant women or lactating women who are breastfeeding or women planning to become
 pregnant during the treatment period.

 -  Serious intercurrent medical illnesses or active infections that, in the investigators
 opinion, might interfere with the interpretation of the study safety data or
 compromise the patients ability to carry out the treatment program.

 -  Known history of seropositivity for HIV or chronic hepatitis (testing for HIV is not
 required).

 -  Known hypersensitivity to ONTAK or any of its components: diptheria toxin,
 interleukin-2 or excipients.

 -  Experimental therapy within 4 weeks prior to study entry.

 -  Patients diagnosed with congestive heart failure, NYHA Class III or IV, ventricular
 tachycardia, fibrillation, or a history of myocardial infarction in the 12 months
 prior to study entry.

 -  Any prior radiation therapy within four weeks of enrollment, or prior radiation
 therapy to the only site of evaluable disease unless disease progression has occurred
 in that site.

 -  Patients on concurrent corticosteroids as treatment for NHL. The use of tapering doses
 or low doses of corticosteroids for resolving GVHD, or the use of corticosteroids as
 premedication prior to ONTAK or as a transient treatment for hypersensitivity
 reactions is permitted as necessary.

 -  History of prior malignancy within the preceding 5 years, except for successfully
 treated cervical carcinoma in situ or basal cell carcinoma.