Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma - Full Text View

Sponsor:	Cancer and Leukemia Group B
Collaborator:	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	Biological: filgrastim Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisone Drug: vincristine sulfate	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized 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:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Etoposide Etoposide phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor Rituximab Vincristine sulfate

U.S. FDA Resources

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:	170
Study Start Date:	May 2005
Estimated Primary Completion Date:	March 2010 (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

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

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 227 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

Additional 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

No publications provided

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:	April 5, 2011
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, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Etoposide phosphate
Doxorubicin
Etoposide

Prednisone
Vincristine
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on February 12, 2012