Clinical trial NCT00005959: Combination Chemotherapy Plus Rituximab in Treating Patients With Intermediate-Grade or High-Grade Non-Hodgkin's Lymphoma
Official title: Phase II Trial of Rituximab in Combination With CHOP Chemotherapy in Patients With Previously Untreated Intermediate or High Grade Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lymphoma
Keywords: stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult Burkitt lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult Burkitt lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-12-17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug with rituximab may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of rituximab plus combination chemotherapy in treating patients who have intermediate-grade or high-grade non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES: I. Determine the rate of complete response and partial response in patients with intermediate or high grade non-Hodgkin's lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). II. Determine the toxicity of this regimen in these patients. III. Determine the disease-free and overall survival, time to response, and time to disease progression in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to the number of risk factors (0-2 vs 3-5). Risk factors include age (no greater than 60 vs greater than 60), tumor stage (II vs III or IV), number of extranodal sites (no more than 1 vs more than 1), performance status (0-1 vs 2-4), and serum LDH level (no greater than normal vs greater than normal). Patients receive rituximab IV on day 1; cyclophosphamide, doxorubicin, and vincristine IV on day 3; and oral prednisone on days 3-7. Patients over 60 also receive filgrastim (G-CSF) subcutaneously beginning on day 4 and continuing until blood counts recover (all other patients receive G-CSF as secondary prophylaxis). Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who respond receive 2 more courses. Patients who have no measurable disease after 6 courses receive rituximab IV once weekly for 4 consecutive weeks. This treatment continues every 6 months for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who have measurable disease after 6 courses of chemotherapy receive 2 more courses for a maximum of 8 courses of CHOP, followed by maintenance therapy with rituximab (as described above). Patients are followed every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed intermediate or high grade non-Hodgkin's lymphoma Stage II, III, or IV disease B-cell where lymphoid cells are CD20 or CD19 positive No mantle cell, lymphoblastic, or peripheral T-cell non-Hodgkin's lymphoma Measurable or evaluable disease No prior treatment for lymphoma No known CNS metastases 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: Karnofsky 60-100% Life expectancy: At least 12 weeks Hematopoietic: Unless documented bone marrow disease: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: SGOT and SGPT no greater than 3 times upper limit of normal Bilirubin no greater than 1.5 mg/dL Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No history of severe heart disease, cardiomyopathy, or congestive heart failure LVEF normal by MUGA or echocardiogram Other: Not pregnant or nursing Fertile patients must use effective contraception No active infection as defined by: Clinical syndrome consistent with a viral or bacterial infection (e.g., influenza, upper respiratory infection, urinary tract infection) OR Fever with a clinical site of infection identified OR Microbiologically documented infection, including, but not limited to, bacteremia or septicemia No known HIV positivity No known sensitivity to E. coli derivatives (e.g., asparaginase, human insulin, human growth hormone, interferon alfa-2b) No other prior malignancy within the past 5 years except surgically cured basal or squamous cell skin cancer or carcinoma in situ of the cervix No psychiatric, addictive, or other disorder that may preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No concurrent biologic therapy except epoetin alfa No white blood cell transfusions Chemotherapy: See Disease Characteristics No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No concurrent radiotherapy Surgery: At least 2 weeks since prior major surgery Other: No other concurrent investigational therapy No prophylactic antibiotics

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: Montgomery Cancer Center
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: Rancho Mirage
country: United States
facility: Cancer and Blood Institute of the Desert
state: California
city: Fort Lauderdale
country: United States
facility: Southeast Florida Hematology-Oncology Group
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Oncology-Hematology Group of South Florida
state: Florida
city: Pensacola
country: United States
facility: Hematology-Oncology Associates, PA
state: Florida
city: Hutchinson
country: United States
facility: Hutchinson Clinic, P.A.
state: Kansas
city: Crestview Hills
country: United States
facility: Hematology/Oncology Care Inc.
state: Kentucky
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders
state: Maine
city: Rockville
country: United States
facility: Associates in Oncology and Hematology
state: Maryland
city: Peabody
country: United States
facility: North Shore Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Medical Center - St. Joseph
state: Michigan
city: Rolla
country: United States
facility: Bond Clinic
state: Missouri
city: Saint Louis
country: United States
facility: Midwest Hematology Oncology Consultants, Ltd.
state: Missouri
city: Morristown
country: United States
facility: Hematology Oncology Associates
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Oncology-Hematology
state: New Mexico
city: Bronx
country: United States
facility: Our Lady of Mercy Medical Center
state: New York
city: Brooklyn
country: United States
facility: HemOnCare, P.C.
state: New York
city: Hickory
country: United States
facility: N.W. Carolina Oncology & Hematology, P.A.
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology/Hematology Care, Inc.
state: Ohio
city: Memphis
country: United States
facility: University of Tennessee, Memphis
state: Tennessee
city: Salt Lake City
country: United States
facility: Intermountain Hematology/Oncology Associates, Inc.
state: Utah
city: Colchester
country: United States
facility: Vermont Center for Cancer Medicine, Inc.
state: Vermont
city: Richmond
country: United States
facility: Hematology & Oncology Associates of Virginia
state: Virginia
Study officials:
affiliation: Amgen
name: Carol Brannan, BS, BSN
role: STUDY_CHAIR
References: