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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:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00460109
First received: April 11, 2007
Last updated: March 7, 2017
Last verified: March 2017
  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 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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 Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Proportion of Confirmed Tumor Response (Complete Response [CR], Unconfirmed CR, and Partial Response) [ Time Frame: Up to 5 years ]
    A confirmed tumor response is defined to be either a CR, CRu or PR. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.


Secondary Outcome Measures:
  • Survival Time [ Time Frame: Up to 5 years ]
    Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

  • Time to Disease Progression [ Time Frame: Up to 5 years ]
    Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier. Progression is defined using the response criteria for non-Hodgkin's lymphoma, as at least a 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PRs or non-responders, or appearance of any new lesion during or at the end of therapy.

  • Duration of Response [ Time Frame: Up to 5 years ]
    Duration of response (DOR) is defined as the time from the date at which the patient's objective status is first noted to be either a CR, CRu or PR to the earliest date of progression. The distribution of DOR will be estimated using Kaplan-Meier methods. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.

  • Time to Subsequent Therapy [ Time Frame: Up to 5 years ]
    Time to subsequent therapy is defined to be the time from the end of active treatment date to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier.


Enrollment: 24
Study Start Date: April 2008
Study Completion Date: March 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rituximab + denileukin diftitox
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.
Biological: denileukin diftitox Biological: rituximab

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   (Adult, Senior)
Sexes Eligible for Study:   All
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
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
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Stephen M. Ansell, MD, PhD Mayo Clinic
  More Information

Publications:
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00460109     History of Changes
Other Study ID Numbers: NCCTG-N0682
NCI-2009-00662 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000539551 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received: April 11, 2007
Results First Received: January 18, 2017
Last Updated: March 7, 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
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
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Denileukin diftitox
Rituximab
Interleukin-2
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 21, 2017