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

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI) Cancer and Leukemia Group B
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003204

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Lymphoma	Drug: cyclophosphamide Drug: prednisone Drug: rituximab Drug: vincristine sulfate	Phase III

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine sulfate Vincristine Fludarabine Fludarabine monophosphate Rituximab Tositumomab Immunoglobulins Globulin, Immune

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Randomized Phase III Study in Low Grade Lymphoma Comparing Cyclophosphamide/Fludarabine to Standard Therapy Followed by Maintenance Anti-CD20 Antibody

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

Estimated Enrollment:	515
Study Start Date:	March 1998

Detailed Description:

OBJECTIVES:

Compare response rate, time to progression, time to treatment failure, and survival of patients with low grade non-Hodgkin's lymphoma treated with a cyclophosphamide and fludarabine regimen (closed as of 9/2000) or standard treatment with cyclophosphamide, vincristine, and prednisone.
Determine the effect of maintenance with rituximab (IDEC-C2B8 monoclonal antibody) on time to progression, times to treatment failure, and survival, as well as its effects on lymphocyte number, subsets, and quantitative immunoglobulin levels over time in these patients.

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.

PROJECTED ACCRUAL: A total of 515 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:

Histologically confirmed stage III-IV low grade non-Hodgkin's lymphoma
- Small lymphocytic
- Follicular small cleaved cell
- Follicular mixed cleaved cell
- Follicular large cell
Measurable disease by at least one of the following:
- Radiographic findings must provide clear-cut measurements
- Bidimensionally measurable, clearly defined defect or mass measuring at least 2 cm in diameter on a radionuclide or CT scan
- An enlarged spleen extending at least 2 cm below the costal margin, provided that no explanation other than lymphomatous involvement is likely
- An enlarged liver with proof of lymphoma in the liver by biopsy
May have low or high tumor burden
- High tumor burden defined as:
  - Nodal or extranodal mass at least 7 cm
  - 3 or more nodal masses greater than 3 cm
  - Systemic symptoms or B symptoms
  - Risk of extrinsic compression of vital organ
  - Leukemia phase with lymphocyte count of greater than 5,000/mm3
  - Absolute neutrophil count less than 1,500/mm3
  - Hemoglobin less than 10 g/dL
  - Platelet count less than 100,000/mm3
Patients with both diffuse and follicular architectural elements are eligible if histology is predominantly follicular (at least 50% of the cross-sectional area)
If diagnosis of low grade non-Hodgkin's lymphoma had been made over 1 year ago, diagnostic confirmation using either fine needle aspiration or nodal biopsy is required NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-1

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics
WBC greater than 3,000/mm^3 (unless documented bone marrow involvement)
Platelet count greater than 100,000/mm^3 (unless documented bone marrow involvement)

Hepatic:

Bilirubin less than 2.0 mg/dL
SGOT no greater than 5 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 5 times ULN

Renal:

Creatinine no greater than 1.5 mg/dL

Other:

No other malignancy within the past 5 years except treated carcinoma in situ of the cervix or basal or squamous cell carcinoma of the skin
No active, uncontrolled infections
Adequate contraception required of all fertile patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior immunotherapy

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003204

Show 54 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Cancer and Leukemia Group B

Investigators

Study Chair:	Howard S. Hochster, MD	New York University School of Medicine
Study Chair:	Stanley R. Frankel, MD	University of Maryland Greenebaum Cancer Center

More Information

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

Publications of Results:

Colocci N, Weller E, Hochster HS, et al.: Prognostic significance of the Follicular Lymphoma International Prognostic Index (FLIPI) in the E1496 trial of chemotherapy with or without maintenance rituximab. [Abstract] J Clin Oncol 23 (Suppl 16): A-6526, 566s, 2005.

Hochster HS, Weller E, Gascoyne RD, et al.: Maintenance rituximab after CVP results in superior clinical outcome in advanced follicular lymphoma (FL): results of the E1496 phase III trial from the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B. [Abstract] Blood 106 (11): A-349, 2005.

Hochster HS, Weller E, Ryan T, et al.: Results of E1496: a phase III trial of CVP with or without maintenance rituximab in advanced indolent lymphoma (NHL). [Abstract] J Clin Oncol 22 (Suppl 14): A-6502, 558s, 2004.

Hochster H, Weller E, Kuzel T, et al.: Increased mortality associated with higher dose cyclophosphamide plus fludarabine (CF) in advanced stage indolent lymphoma patients treated on E1496, an Eastern Cooperative Oncology Group (ECOG) and CALGB study. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1125, 2002.

Study ID Numbers:	CDR0000066056, E-1496, CLB-59902
Study First Received:	May 2, 2000
Last Updated:	August 23, 2008
ClinicalTrials.gov Identifier:	NCT00003204
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 III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma

stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Prednisone
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Vincristine
Fludarabine monophosphate
Cyclophosphamide

Antibodies, Monoclonal
Lymphatic Diseases
Antibodies
Leukemia, Lymphocytic, Chronic, B-Cell
Fludarabine
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Follicular lymphoma
Immunoglobulins

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antimitotic Agents
Hormones

Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009