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

This study has been completed.
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: April 11, 2007
Last updated: August 22, 2012
Last verified: April 2010

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Combinations of biological substances in denileukin diftitox may be able to carry cancer-killing substances directly to cancer cells. Giving rituximab together with denileukin diftitox may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with denileukin diftitox works in treating patients with previously untreated stage III or stage IV follicular B-cell non-Hodgkin's lymphoma.

Condition Intervention Phase
Biological: denileukin diftitox
Biological: rituximab
Other: flow cytometry
Other: immunoenzyme technique
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial of Denileukin Diftitox in Combination With Rituximab in Previously Untreated Follicular B-Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of confirmed tumor response (complete response [CR], unconfirmed CR, and partial response) [ Designated as safety issue: No ]
  • Proportion of successes [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival time [ Designated as safety issue: No ]
  • Time to disease progression [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time to subsequent therapy [ Designated as safety issue: No ]
  • Changes in immunologic parameters [ Designated as safety issue: No ]
  • Incidence of immune responses [ Designated as safety issue: No ]

Estimated Enrollment: 53
Study Start Date: April 2008
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Detailed Description:



  • 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.
  • Assess the overall survival, time-to-progression, duration of response, and time-to-new therapy in patients treated with this regimen.


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

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.

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


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • No prior chemotherapy, immunotherapy, vaccines, or radiotherapy for NHL
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00460109

  Show 165 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Study Chair: Stephen M. Ansell, MD, PhD Mayo Clinic
Investigator: Thomas E. Witzig, MD Mayo Clinic
Investigator: Peter T. Silberstein, MD Creighton University Medical Center
  More Information

Additional Information:
Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00460109     History of Changes
Other Study ID Numbers: CDR0000539551, NCCTG-N0682
Study First Received: April 11, 2007
Last Updated: August 22, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Denileukin diftitox
Analgesics, Non-Narcotic
Antineoplastic Agents
Antirheumatic Agents
Central Nervous System Agents
Immunologic Factors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 01, 2015