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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.
Verified by National Cancer Institute (NCI), January 2009
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00118209
  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.

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
 Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: filgrastim
Drug: prednisone
Drug: rituximab
Drug: vincristine sulfate
 Phase III

MedlinePlus related topics: Cancer Lymphoma
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Filgrastim Etoposide Prednisone Vincristine sulfate Vincristine Rituximab Etoposide phosphate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
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

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: 478
Study Start Date: May 2005
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I (R-CHOP): Active Comparator
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.
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: rituximab
Given IV
Drug: vincristine sulfate
Prednisone given orally; all others given IV
Arm II (EPOCH-R): Experimental
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.
Drug: cyclophosphamide
Prednisone given orally; all others given IV
Drug: doxorubicin hydrochloride
Prednisone given orally; all others given IV
Drug: etoposide
Given IV
Drug: filgrastim
No administration information available
Drug: prednisone
Prednisone given orally; all others given IV
Drug: rituximab
Given IV
Drug: vincristine sulfate
Prednisone given orally; all others given IV

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.
  • Determine the use of molecular profiling for pathological diagnosis in patients treated with these regimens.

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.

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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00118209

  Show 164 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
National Cancer Institute (NCI)
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

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

Study ID Numbers: CDR0000433265, CALGB-50303, ECOG-50303, NCI-05-C-0252
Study First Received: July 8, 2005
Last Updated: January 15, 2009
ClinicalTrials.gov Identifier: NCT00118209  
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

Study placed in the following topic categories:
Prednisone
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Lymphoma, small cleaved-cell, diffuse
Vincristine
Cyclophosphamide
Etoposide phosphate
Doxorubicin
 Lymphoma, B-Cell
Lymphoma, large-cell
Lymphatic Diseases
B-cell lymphomas
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Etoposide
Lymphoma

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
Antibiotics, Antineoplastic
 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



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