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

Sponsors and Collaborators:	North Central Cancer Treatment Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00460109

Purpose

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
Lymphoma	Biological: denileukin diftitox Biological: rituximab Other: flow cytometry Other: immunoenzyme technique Other: laboratory biomarker analysis	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Denileukin diftitox Rituximab

U.S. FDA Resources

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
Estimated Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Eligibility

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

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

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

Contacts and Locations

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

Show 140 Study Locations

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	North Central Cancer Treatment Group ( Jan C. Buckner )
Study ID Numbers:	CDR0000539551, NCCTG-N0682
Study First Received:	April 11, 2007
Last Updated:	June 25, 2009
ClinicalTrials.gov Identifier:	NCT00460109 History of Changes
Health Authority:	Unspecified

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

Study placed in the following topic categories:

Immunoproliferative Disorders
Immunologic Factors
Rituximab
Lymphoma, Follicular
Follicular Lymphoma
Lymphoma, B-Cell
Lymphoma, Small Cleaved-cell, Diffuse
Lymphatic Diseases
B-cell Lymphomas

Analgesics, Non-Narcotic
Interleukin-2
Denileukin diftitox
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Immunologic Factors
Immune System Diseases
Rituximab
Antineoplastic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Lymphoma, B-Cell
Lymphatic Diseases
Neoplasms
Sensory System Agents

Analgesics, Non-Narcotic
Interleukin-2
Therapeutic Uses
Denileukin diftitox
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Central Nervous System Agents
Lymphoma

ClinicalTrials.gov processed this record on July 06, 2009