Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With Stage III or Stage IV Low-Grade Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003204
First received: May 2, 2000
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

Randomized phase III trial to compare the effectiveness of two regimens of combination chemotherapy followed by rituximab or observation in treating patients who have stage III or stage IV low-grade non-Hodgkin's lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known which regimen of combination chemotherapy, with or without rituximab, is more effective for non-Hodgkin's lymphoma


Condition Intervention Phase
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Small Lymphocytic Lymphoma
Drug: cyclophosphamide
Drug: fludarabine phosphate
Drug: vincristine sulfate
Drug: prednisone
Biological: rituximab
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase III Study in Low Grade Lymphoma Comparing Maintenance Anti-CD20 Antibody Versus Observation Following Induction Therapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time to treatment failure [ Time Frame: From maintenance randomization to the earlier of progression or death, assessed up to 5 years ] [ Designated as safety issue: No ]
    This comparison will be made using a one-sided logrank test with a 5% type I error rate.


Enrollment: 515
Study Start Date: March 1998
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (cyclophosphamide, fludarabine)
Patients receive cyclophosphamide IV over 30-45 minutes on day 1 and fludarabine IV over 10-20 minutes on days 1-5. Treatment repeats every 28 days in the absence of disease progression for a minimum of 4 courses and a maximum of 6 courses.
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (cyclophosphamide, vincristine, prednisone)
Patients receive cyclophosphamide IV over 30-45 minutes and vincristine IV on day 1, and oral prednisone on days 1-5. Treatment repeats every 21 days in the absence of disease progression for a minimum of 6 courses and a maximum of 8 courses.
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (rituximab)
Patients receive maintenance therapy with rituximab (IDEC-C2B8 monoclonal antibody) IV weekly for 4 weeks. Courses repeat every 6 months for 2 years. Maintenance therapy begins 4 weeks after the last chemotherapy.
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Other: laboratory biomarker analysis
Correlative studies
No Intervention: Arm IV (no intervention)
Patients undergo no maintenance therapy and are observed. Patients are followed every 3 months for 2 years, every 6 months for the next 3 years, and then annually thereafter.

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the response rate, time to progression, time to treatment failure, and survival for patients with low grade lymphoma treated with the cyclophosphamide - fludarabine regimen with a control arm consisting of standard treatment with CVP.

II. To determine the effect of maintenance with anti-CD20 (IDEC C2B8) on time to progression, time to treatment failure, and survival and its effects on lymphocyte number, subsets, and quantitative immunoglobulin levels over time.

OUTLINE: This a two step, stratified, randomized study. Patients are stratified for arms I and II (step 1) by age (under 60 vs 60 and over), tumor burden (high vs low), histology (follicular vs other), and B symptoms (present vs absent). After arms I and II have been completed, patients are stratified in arms III and IV (step 2) by extent of residual disease (minimal vs gross), histology (follicular vs other), and initial tumor burden.

ARM I (CLOSED AS OF 9/2000): Patients receive cyclophosphamide IV over 30-45 minutes on day 1 and fludarabine IV over 10-20 minutes on days 1-5. Treatment repeats every 28 days in the absence of disease progression for a minimum of 4 courses and a maximum of 6 courses.

ARM II: Patients receive cyclophosphamide IV over 30-45 minutes and vincristine IV on day 1, and oral prednisone on days 1-5. Treatment repeats every 21 days in the absence of disease progression for a minimum of 6 courses and a maximum of 8 courses.

After completion of therapy on arm I or II, patients are randomized into step 2 of this study comprising arms III and IV.

ARM III: Patients receive maintenance therapy with rituximab (IDEC-C2B8 monoclonal antibody) IV weekly for 4 weeks. Courses repeat every 6 months for 2 years. Maintenance therapy begins 4 weeks after the last chemotherapy.

ARM IV: Patients undergo no maintenance therapy and are observed.

Patients are followed every 3 months for 2 years, every 6 months for the next 3 years, and then annually thereafter.

  Eligibility

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

Inclusion Criteria:

  • Patients must have Stage III-IV (Ann Arbor classification) low-grade Non-Hodgkin's lymphoma
  • Baseline measurements and evaluations must be obtained within 4 weeks prior to registration; all areas of disease (evaluable and measurable) should be recorded and mapped out in order to assess response and uniformity of response to therapy; must have at least one objective MEASURABLE disease parameter

    • Radiographic findings are acceptable providing that clear-cut measurement can be made
    • Abnormalities on scans may be used to document the presence of disease for staging purposes; a clearly defined, bidimensionally measurable defect or mass measuring at least 2 cm in diameter on a radionuclide or a CT scan will be acceptable as measurable disease
    • An enlarged spleen extending at least 2 cm below the costal margin will constitute measurable disease providing that no explanation other than lymphomatous involvement is likely; for an enlarged liver to constitute the only evident measurable disease parameter, liver biopsy proof of lymphoma in the liver is required
  • Patients must have a tissue diagnosis of low-grade malignant lymphoma obtained within 12 months prior to registration (according to the International Working Formulation) as below:

    • ML- small lymphocytic (Category A)
    • ML-follicular-small cleaved (Category B)
    • ML-follicular-mixed small cleaved and large cell (Category C)
  • Patients having both diffuse and follicular architectural elements will be considered eligible if the histology is predominantly follicular (i.e. >= 50% of the cross-sectional area); if the interval since tissue diagnosis of low-grade malignant lymphoma is > 12 months, diagnostic confirmation using either FNA or nodal biopsy is required to confirm that the histology remains in one of the eligible categories
  • Women of child bearing potential and sexually active males are strongly advised to use an accepted and effective method of birth control
  • No prior chemotherapy, radiotherapy, or immunotherapy
  • No active, uncontrolled infections (afebrile for > 48 hours off antibiotics)
  • No evidence of a previous or concurrent malignancy, with the exception of 1) treated carcinoma in situ of the cervix, 2) treated squamous cell or basal cell skin cancer OR 3) any other surgically cured malignancy from which the patient has been disease free for at least 5 years
  • ECOG performance status 0-1
  • WBC > 3000/mm^3
  • Plts > 100,000/mm^3
  • Creatinine =< 1.5 mg/dl
  • Bilirubin < 2.0 mg/dl
  • LFTs =< 5x ULN (SGOT and Alkaline Phosphate)
  • These lab values must be obtained within 4 weeks prior to protocol entry; patients with documented marrow involvement at the time of registration are not required to meet the hematologic parameters above
  • Patient must give signed informed consent
  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: NCT00003204

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Howard Hochster Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003204     History of Changes
Other Study ID Numbers: NCI-2012-02972, E1496, U10CA021115, CDR0000066056
Study First Received: May 2, 2000
Last Updated: February 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Cyclophosphamide
Fludarabine monophosphate
Rituximab
Fludarabine
Prednisone
Vincristine
Vidarabine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 22, 2014