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

Alternate Title

Rituximab and Denileukin Diftitox in Treating Patients With Previously Untreated Stage III or Stage IV Follicular B-Cell Non-Hodgkin's Lymphoma

Basic Trial Information

Objectives

Primary

1. Determine the response rate (complete response [CR], unconfirmed CR, and partial response) in patients with previously untreated stage III or IV follicular B-cell non-Hodgkin's lymphoma treated with rituximab and denileukin diftitox.
2. Assess the overall survival, time-to-progression, duration of response, and time-to-new therapy in patients treated with this regimen.

Secondary

1. Determine whether this regimen depletes or inhibits the function of regulatory T cells in these patients.

Entry Criteria

Disease Characteristics:

• Pathologically confirmed follicular B-cell non-Hodgkin's lymphoma (NHL)
  • Stage III or IV disease
  • Grade 1 or 2 disease

• Previously untreated disease

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
  • Clearly defined bidimensional diameter ≥ 2 x 2 cm on physical examination OR > 2.0 cm in 1 of the dimensions by CT scan, MRI, or plain radiograph imaging
  • Splenic enlargement may be used as a measurable parameter if the spleen is palpable ≥ 3 cm below the left costal margin

• Circulating tumor cells < 5,000/mm³

• Must have paraffin-embedded tissue blocks/slides available

• No CNS lymphoma

Prior/Concurrent Therapy:

• No prior chemotherapy, immunotherapy, vaccines, or radiotherapy for NHL

Patient Characteristics:

• ECOG performance status 0-2
• Life expectancy ≥ 1 year
• WBC ≥ 3,400/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10.0 g/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 times ULN
• AST ≤ 3 times ULN
• Creatinine ≤ 1.5 times ULN
• Albumin ≥ 3 g/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 year after completion of study therapy
• No HIV infection
• No other active malignancies
• No active uncontrolled infection
• No known hypersensitivity to denileukin diftitox or any of its components, including diphtheria toxin, aldesleukin, or excipients

Expected Enrollment

A total of 53 patients will be accrued for this study.

Outcomes

Proportion of confirmed tumor response (complete response [CR], unconfirmed CR, and partial response)
Proportion of successes

Survival time
Time to disease progression
Duration of response
Time to subsequent therapy
Changes in immunologic parameters
Incidence of immune responses

Outline

This is a multicenter study.

Patients receive rituximab IV on days 1, 8, 15, and 22. Patients also receive denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Blood is collected at baseline; on day 1 of courses 2-4; and 1 and 4 months after completion of study treatment for research studies. Research studies include analysis of peripheral blood lymphocyte subsets expressing CD3, CD4, CD8, CD19, CD25, and CD26 by flow cytometry; quantitation of CD4+, CD25+ regulatory T cells by flow cytometry; tumor-specific γ-interferon-secreting T cells by enzyme-linked immunospot assay; tumor-specific cytotoxic T-lymphocyte activity; and immune activation by enzyme-linked immunosorbent assay.

After completion of study treatment, patients are followed periodically for up to 5 years after registration.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Stephen Ansell, MD, PhD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Thomas Witzig, MD, Protocol co-chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Peter Silberstein, MD, Protocol co-chair		Ph: 402-280-4364 Email: psilberstein@creighton.edu

Registry Information
Official Title		A Phase II Clinical Trial of Denileukin Diftitox in Combination with Rituximab in Previously Untreated Follicular B-Cell Non-Hodgkin's Lymphoma
Trial Start Date		2008-04-04
Trial Completion Date		2011-03-15
Registered in ClinicalTrials.gov		NCT00460109
Date Submitted to PDQ		2007-03-13
Information Last Verified		2010-04-10
NCI Grant/Contract Number		CA25224

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