Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma
Basic Trial Information
|Phase III||Diagnostic, Treatment||Closed||18 and over||NCI, Other||CALGB-50303|
CDR0000433265, NCI-2009-00480, U10CA031946, U10CA180821, ECOG-50303, NCI-05-C-0252, NCT00118209
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. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell lymphoma.
PURPOSE: This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma.
Further Study Information
1. Primary Objectives:
1. To compare the event-free survival of R-CHOP versus DA-EPOCH-R chemotherapy in untreated CD20+ diffuse large B-cell lymphomas
2. To develop a molecular predictor of outcome of R-CHOP and DA-EPOCH-R chemotherapy using molecular profiling
2. Secondary Objectives:
1. To compare the response rates, overall survival and toxicity of R-CHOP versus DA-EPOCH-R
2. To define the pharmacogenomics of untreated DLBCL and correlate clinical parameters (toxicity, response, survival outcomes and laboratory results) with molecular profiling
3. To assess the use of molecular profiling for pathological diagnosis
4. To identify new therapeutic targets using molecular profiling
5. To perform a comprehensive analysis of somatic alterations to the tumor genome and to understand which genomic alterations are somatically acquired by the tumor and which are encoded in the germ line of the patient
6. To identify biomarkers of response to chemotherapy by FDG-PET/CT imaging that are predictive of histopathologic remissions and survival in patients with stage I (mediastinal), II, III, or IV untreated DLBCL
7. To evaluate the use of semiquantitative measurements of FDG uptake in defining FDG-PET/CT based biomarkers of response to chemotherapy in patients with DLBCL
8. To determine whether FDG-PET/CT measurements of tumor response after the second cycle of chemotherapy can predict clinical response
9. To establish a standardized protocol for FDG-PET/CT image acquisition
10. To determine additional FDG-PET/CT parameters (e.g., the ratio of tumor SUVmax to liver SUVmean; SUVs corrected for body surface area and lean body mass; nuclear medicine physician's assessment) and evaluate their utility in refining FDG-PET/CT based biomarkers of response to therapy
11. To evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication
After patients have completed treatment on this study, all patients will be asked to return to the clinic for follow-up exams every three months for the first two years, and then every six months thereafter for three years. A total of five years from study registration.
1. Histologically documented de novo CD20+ DLBCL with stage II, III or IV disease.
- Stage I primary mediastinal (thymic) DLBCL is also eligible.
- Patients with an underlying low-grade lymphoma, such as a transformed lymphoma or low-grade lymphoma in the bone marrow, are not eligible.
- Diagnosis should be based on an adequate tissue sample, including open biopsy or core needle biopsy.
- Needle aspiration for primary diagnosis is unacceptable.
- Patients must have one of the following WHO classification subtypes:
- Diffuse large B-cell lymphoma (includes morphological variants: centroblastic, immunoblastic, T-cell/histiocyte rich, and anaplastic)
- Mediastinal (thymic) large B-cell lymphoma
- Intravascular large B-cell lymphoma
- Note: Failure to submit a pathology block within 60 days of patient registration will be considered a major protocol violation.
- Fresh (frozen) tumor biopsy must be available or attempted. A frozen tumor biopsy equivalent to a minimum of four at least 16 gauge needle cores is an important component of this study.
- Patients without adequate frozen material should have a biopsy performed to obtain material.
- If a biopsy is performed and does not yield adequate material, the patient is still eligible for the study. If a biopsy cannot be done safely, the patient may still be eligible for the study if permission is granted.
- Note: This study does not allow concurrent radiation unless a patient has a documented CNS treatment failure with no systemic failure.
2. No prior cytotoxic chemotherapy or rituximab. Patients may be entered if they have received prior limited field radiation therapy or a short course of glucocorticoids (< 10 days) for an urgent local disease complication at diagnosis (e.g., cord compression, SVC syndrome). Patients who have received chemotherapy for prior malignancies are not eligible.
3. Age ≥ 18 years
4. ECOG Performance Status 0-2
5. No active ischemic heart disease or congestive heart failure. If there is suspicion of cardiac disease, a cardiac ejection fraction must show LVEF > 45%, but the study is not required
6. No known lymphomatous involvement of the CNS. A lumbar puncture prior to study is not required in the absence of neurological symptoms
7. No known HIV disease. Patients with a history of intravenous drug abuse or any other behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. Patients who test positive or who are known to be infected are not eligible.
8. Non pregnant and non-nursing. Treatment would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective form of contraception.
9. Patients with active medical processes (e.g., uncontrolled bacterial or viral infection, bleeding) not related to their lymphoma should be excluded.
10. Required Initial Laboratory Values (unless non-Hodgkin lymphoma):
- ANC ≥ 1000/μL
- Platelets ≥ 100,000/μL
- Creatinine≤ 1.5 mg/dL or creatinine clearance ≥ 50 cc/min
- Total Bilirubin ≤ 2 mg/dL (unless a history of Gilbert's Disease)
Trial Contact Information
Trial Lead Organizations/Sponsors
Alliance for Clinical Trials in Oncology
- National Cancer Institute
Northridge Hospital Medical Center
Sheldon J. Davidson
Phoebe Cancer Center at Phoebe Putney Memorial Hospital
Jose M. Tongol
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
O. George Negrea
Louis A. Weiss Memorial Hospital
Keith L. Shulman
Ochsner Health Center - Bluebonnet
Charles V Wendling
Ochsner Health Center - Covington
Charles V Wendling
CCOP - Ochsner
Charles V Wendling
University of Mississippi Cancer Clinic
Vincent E Herrin
Big Sky Oncology
Grant William Harrer
St. Joseph's Hospital and Medical Center
Providence Centralia Hospital
St. Francis Hospital
St. Clare Hospital
Providence St. Peter Hospital Regional Cancer Center
Good Samaritan Cancer Center
CCOP - Northwest
Franciscan Cancer Center at St. Joseph Medical Center
MultiCare Regional Cancer Center at Tacoma General Hospital
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00118209
ClinicalTrials.gov processed this data on April 09, 2015
Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.