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

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