Trial record 1 of 1 for:    CALGB 50303
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Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00118209
First received: July 8, 2005
Last updated: February 13, 2013
Last verified: February 2013
  Purpose

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 non-Hodgkin's lymphoma. Imaging procedures, such as fludeoxyglucose F 18 positron emission tomography (FDG-PET)/computed tomography (CT), may help diagnose if recurrent disease is likely.

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 non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: prednisone
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event-free survival 5 years after completion of study treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • R-CHOP and DA-EPOCH-R molecular predictors of outcome as measured by cDNA microarray 5 years after completion of study treatment [ Designated as safety issue: No ]

Estimated Enrollment: 523
Study Start Date: May 2005
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (R-CHOP)
Patients receive rituximab IV, cyclophosphamide IV, doxorubicin IV over 3-5 minutes, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Biological: rituximab
Given IV
Drug: cyclophosphamide
Prednisone given orally; all others given IV
Drug: doxorubicin hydrochloride
Prednisone given orally; all others given IV
Drug: prednisone
Prednisone given orally; all others given IV
Drug: vincristine sulfate
Prednisone given orally; all others given IV
Experimental: Arm II (EPOCH-R)
Patients receive rituximab IV on day 1, doxorubicin IV, etoposide IV, and vincristine IV continuously over 96 hours on days 1-4, cyclophosphamide IV on day 5, and oral prednisone twice daily on days 1-5. Patients also receive filgrastim (G-CSF) once daily on days 2-11 or until blood counts recover. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Biological: filgrastim
No administration information available
Biological: rituximab
Given IV
Drug: cyclophosphamide
Prednisone given orally; all others given IV
Drug: doxorubicin hydrochloride
Prednisone given orally; all others given IV
Drug: etoposide
Given IV
Drug: prednisone
Prednisone given orally; all others given IV
Drug: vincristine sulfate
Prednisone given orally; all others given IV

  Hide Detailed Description

Detailed Description:

OBJECTIVES:

Primary

  • Compare the event-free survival of patients with previously untreated de novo diffuse large B-cell non-Hodgkin's lymphoma treated with R-CHOP comprising rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone vs EPOCH-R comprising etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab.
  • Determine molecular predictors of outcome (using molecular profiling) in patients treated with these regimens.

Secondary

  • Compare the response rate and overall survival of patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.
  • Correlate the clinical parameters (i.e., toxicity, response, survival outcomes, and laboratory results) with molecular profiling in patients treated with these regimens.
  • Assess the use of molecular profiling for pathological diagnosis in patients treated with these regimens.
  • Identify new therapeutic targets using molecular profiling.
  • Perform a comprehensive analysis of somatic alterations to the tumor genome in order to understand which genomic alterations are somatically acquired by the tumor and which are encoded in the germ line of the patient.
  • 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.
  • Evaluate the use of semiquantitative measurements of FDG uptake in defining FDG-PET/CT-based biomarkers of response to chemotherapy in patients with DLBCL.
  • Determine whether FDG-PET/CT measurements of tumor response after the second cycle of chemotherapy can predict clinical response.
  • Establish a standardized protocol for FDG-PET/CT image acquisition.
  • 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.
  • Evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to International Prognostic Index score. Patients are randomized to 1 of 2 treatment arms.

  • Arm I (R-CHOP): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin IV over 3-5 minutes, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II (EPOCH-R): Patients receive rituximab IV on day 1, doxorubicin IV, etoposide IV, and vincristine IV continuously over 96 hours on days 1-4, cyclophosphamide IV on day 5, and oral prednisone twice daily on days 1-5. Patients also receive filgrastim (G-CSF) once daily on days 2-11 or until blood counts recover. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

As of July 1, 2012, the FDG-PET/CT imaging companion study CALGB-580603 will be required of all patients enrolling on this study. FDG-PET/CT scans of abdomen/chest/pelvis are collected at baseline, post-course 2, and post-course 6.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 478 patients (239 per treatment arm) will be accrued for this study within 4.5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed* de novo B-cell non-Hodgkin's lymphoma (NHL) of 1 of the following WHO histologic subtypes:

    • Diffuse large cell lymphoma, including any of the following morphologic variants:

      • Centroblastic
      • Immunoblastic
      • T-cell/histiocyte rich
      • Anaplastic
    • Mediastinal (thymic) large cell lymphoma
    • Intravascular large cell lymphoma NOTE: *Fine needle aspirates or core biopsies must not be the only diagnostic material
  • Stage I primary mediastinal (thymic) OR stage II-IV disease
  • CD20-positive disease
  • No underlying low-grade lymphoma (e.g., transformed lymphoma or low-grade lymphoma in the bone marrow)
  • No known lymphomatous CNS involvement

    • Lumbar puncture required unless there are no neurological symptoms
  • As of July 1, 2012, the PET/CT imaging companion study CALGB-580603 will be required of all patients enrolling onto the treatment study CALGB-50303 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 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3^*
  • Platelet count ≥ 100,000/mm^3^*
  • No active bleeding unrelated to NHL NOTE: *Unless due to NHL

Hepatic

  • Bilirubin ≤ 2 mg/dL* NOTE: *Unless due to NHL or Gilbert's disease

Renal

  • Creatinine ≤ 1.5 mg/dL^* OR
  • Creatinine clearance ≥ 50 mL/min^* NOTE: *Unless due to NHL

Cardiovascular

  • No active ischemic heart disease
  • No congestive heart failure

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No active uncontrolled bacterial or viral infection unrelated to NHL
  • No other active medical process unrelated to NHL

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior rituximab

Chemotherapy

  • No prior chemotherapy for other malignancies
  • No prior cytotoxic chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Prior short course (< 10 days) glucocorticoids allowed for an urgent local disease complication (e.g., cord compression or superior vena cava syndrome) at diagnosis
  • No concurrent hormonal therapy except steroids for adrenal failure or hormones for non-disease related conditions (e.g., insulin for diabetes)
  • No concurrent dexamethasone or other steroidal antiemetics

Radiotherapy

  • Prior limited field radiotherapy allowed for an urgent local disease complication (e.g., cord compression or superior vena cava syndrome) at diagnosis
  • No concurrent radiotherapy except for isolated CNS lesions

Surgery

  • Not specified

Other

  • No other concurrent investigational or commercial agents or therapies for NHL
  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: NCT00118209

  Show 46 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Wyndham H. Wilson, MD, PhD National Cancer Institute (NCI)
Investigator: Andrew D. Zelenetz, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00118209     History of Changes
Obsolete Identifiers: NCT00234351
Other Study ID Numbers: CDR0000433265, CALGB-50303, ECOG-50303, NCI-05-C-0252
Study First Received: July 8, 2005
Last Updated: February 13, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I adult diffuse large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Doxorubicin
Etoposide
Liposomal doxorubicin
Prednisone
Rituximab
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on October 23, 2014