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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: denileukin diftitox


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: denileukin diftitox|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective clinical response (complete or partial response) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  |  | 
| Overall survival at 1 year |  |  | 
| Safety |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult diffuse large cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent small lymphocytic lymphoma