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.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00460109
First received: April 11, 2007
Last updated: August 22, 2012
Last verified: April 2010

April 11, 2007
August 22, 2012
April 2008
October 2010   (final data collection date for primary outcome measure)
  • 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 ]
  • Proportion of confirmed tumor response (complete response [CR], unconfirmed CR, and partial response)
  • Proportion of successes
Complete list of historical versions of study NCT00460109 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Survival time
  • Time to disease progression
  • Duration of response
  • Time to subsequent therapy
  • Changes in immunologic parameters
  • Incidence of immune responses
Not Provided
Not Provided
 
Rituximab and Denileukin Diftitox in Treating Patients With Previously Untreated Stage III or Stage IV Follicular B-Cell Non-Hodgkin's Lymphoma
A Phase II Clinical Trial of Denileukin Diftitox in Combination With Rituximab in Previously Untreated Follicular B-Cell Non-Hodgkin's Lymphoma

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.

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Interventional
Phase 2
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • Biological: denileukin diftitox
  • Biological: rituximab
  • Other: flow cytometry
  • Other: immunoenzyme technique
  • Other: laboratory biomarker analysis
Not Provided
Ansell SM, Tang H, Kurtin PJ, Koenig PA, Nowakowski GS, Nikcevich DA, Nelson GD, Yang Z, Grote DM, Ziesmer SC, Silberstein PT, Erlichman C, Witzig TE. Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma. Leukemia. 2012 May;26(5):1046-52. doi: 10.1038/leu.2011.297. Epub 2011 Oct 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
53
Not Provided
October 2010   (final data collection date for primary outcome measure)

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

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

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, immunotherapy, vaccines, or radiotherapy for NHL
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00460109
CDR0000539551, NCCTG-N0682
Not Provided
Jan C. Buckner, North Central Cancer Treatment Group
North Central Cancer Treatment Group
National Cancer Institute (NCI)
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
National Cancer Institute (NCI)
April 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP