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

NCT00003204 | Completed Phase 3

• 4 other identifiers: NCI-2012-02972E1496U10CA021115CDR0000066056
• Study Type: interventional
• Target: 515
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Time to treatment failure

  This comparison will be made using a one-sided logrank test with a 5% type I error rate.

  From maintenance randomization to the earlier of progression or death, assessed up to 5 years

Study Arms (4)

Arm I (cyclophosphamide, fludarabine)

EXPERIMENTAL

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; Drug: fludarabine phosphate; Other: laboratory biomarker analysis

Arm II (cyclophosphamide, vincristine, prednisone)

EXPERIMENTAL

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; Drug: vincristine sulfate; Drug: prednisone; Other: laboratory biomarker analysis

Arm III (rituximab)

EXPERIMENTAL

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; Other: laboratory biomarker analysis

Arm IV (no intervention)

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.

Interventions

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Arm I (cyclophosphamide, fludarabine); Arm II (cyclophosphamide, vincristine, prednisone)

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Arm I (cyclophosphamide, fludarabine)

vincristine sulfate DRUG

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS

Arm II (cyclophosphamide, vincristine, prednisone)

prednisone DRUG

Given PO

Also known as: DeCortin, Deltra

Arm II (cyclophosphamide, vincristine, prednisone)

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Arm III (rituximab)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (cyclophosphamide, fludarabine); Arm II (cyclophosphamide, vincristine, prednisone); Arm III (rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Eastern Cooperative Oncology Group

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cyclophosphamide; fludarabine phosphate; Vincristine; Prednisone; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Howard Hochster

  Eastern Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2000
• First Posted: January 27, 2003
• Study Start: March 1, 1998
• Primary Completion: May 1, 2006
• Last Updated: February 27, 2013

Record last verified: 2013-02

Locations

US (1)