A Phase II Multicenter Study of Ontak® (Denileukin Diftitox) in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

Inclusion 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