Denileukin Diftitox in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Denileukin Diftitox in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
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.
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