Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	E-1497 NCT00003615, E1497

Objectives

I.   Determine the objective response rate in patients with previously treated stage I, II, III, or IV low- or intermediate-grade B-cell 
non-Hodgkin's lymphoma treated with denileukin diftitox.

II.  Determine the time to progression, duration of remission, and time to 
treatment failure in patients after treatment with this therapy.

III. Determine the toxicity of this therapy in these patients.

IV.  Correlate the results of the inteleukin-2 receptor assay with treatment outcomes in these patients.

Entry Criteria

Disease Characteristics:

Histologically proven stage I, II, III, or IV low- or intermediate-grade B-cell non-Hodgkin's lymphoma
 Small lymphocytic 
 Follicular small cleaved cell 
 Follicular mixed cell 
 Follicular large cell 
 Marginal 
 Diffuse large B-cell
 Lymphoplasmacytoid 

 Patients with small lymphocytic lymphoma must have an absolute lymphocyte
 count less than 10,000/mm3

At least one bidimensionally measurable site
 At least 1.5 cm in its greatest dimension
 Not in field of prior radiotherapy

Progressive disease after at least one prior treatment regimen for lymphoma

A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma.  However, this protocol uses the former terminology.

Prior/Concurrent Therapy:

Biologic therapy:
 Prior stem cell transplantation allowed
 At least 4 weeks since prior biologic therapy
 No other concurrent immunotherapy

Chemotherapy:
 At least 4 weeks since prior chemotherapy
 No concurrent chemotherapy

Endocrine therapy:
 At least 4 weeks since prior endocrine therapy
 No concurrent hormonal therapy (except contraceptives and replacement
  steroids)
 No concurrent corticosteroids

Radiotherapy:
 See Disease Characteristics
 At least 4 weeks since prior radiotherapy for localized disease
 No concurrent radiotherapy

Surgery:
 Not specified

Other:
 No other concurrent experimental medications (including approved drugs tested in an
  investigational setting)

Patient Characteristics:

Age:
 18 and over

Performance status:
 ECOG 0-2

Life expectancy:
 Not specified

Hematopoietic:
 See Disease Characteristics
 Absolute neutrophil count at least 1000/mm3
 Platelet count at least 50,000/mm3
 Hemoglobin at least 8 g/dL

Hepatic:
 Bilirubin no greater than 1.5 times upper limit of normal (ULN)
 ALT or AST no greater than 2 times ULN
 Albumin greater than 3.0 g/dL
 No hepatitis B or C infection

Renal:
 Creatinine no greater than ULN

Other:
 Not pregnant or nursing
 Fertile patients must use effective contraception
 HIV negative
 No active infection requiring anti-infective therapy
 No other prior invasive malignancy within past 5 years, except:
  Curatively treated basal cell or squamous cell skin cancer
  Carcinoma in situ of the cervix 

Expected Enrollment

A total of 33 patients will be accrued for the interleukin-2 (IL-2) receptor-positive stratum and a total of 
11-44 patients will be accrued for the IL-2 receptor-negative stratum.

Outline

Patients are stratified according to interleukin-2 receptor classification (positive vs 
negative).

Patients receive immunotoxin therapy with denileukin diftitox IV over 15-60 
minutes on days 1-5. Treatment repeats every 21 days for 2-6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Kuzel TM, Li S, Eklund J, et al.: Phase II study of denileukin diftitox for previously treated indolent non-Hodgkin lymphoma: final results of E1497. Leuk Lymphoma 48 (12): 2397-402, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Timothy Kuzel, MD, Protocol chair		Ph: 312-695-6180

Registry Information
Official Title		A Phase II Study of DAB 389 IL-2, an Interleukin-2 Fusion Toxin, for Previously Treated Stage II, III, and IV Follicular Low-Grade Non-Hodgkin's Lymphoma
Trial Start Date		1999-03-04
Trial Completion Date		2008-12-15
Registered in ClinicalTrials.gov		NCT00003615
Date Submitted to PDQ		1998-10-02
Information Last Verified		2009-02-16
NCI Grant/Contract Number		U10-CA21115