Combination Chemotherapy and Monoclonal Antibody Therapy in Treating Patients With Non-Hodgkin's Lymphoma - Full Text View

Sponsor:	Cancer and Leukemia Group B
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00032019

Purpose

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

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy in treating patients who have previously untreated 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 II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Study Of Dose-Adjusted Epoch-Rituximab (EPOCH-R) Chemotherapy For Patients With Previously Untreated Aggressive CD20+ B-Cell Non-Hodgkin's Lymphoma (NHL)

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 Immunoglobulins Vincristine sulfate Globulin, Immune

U.S. FDA Resources

Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:

Response [ Time Frame: 5 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression free Survival [ Time Frame: Study entry to progression or tx related death ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: Study entry to death from any cause ] [ Designated as safety issue: No ]
Toxicity [ Time Frame: q 2cycles on Tx, then q 6 mon for 2 yrs, then at relapse ] [ Designated as safety issue: Yes ]

Enrollment:	78
Study Start Date:	February 2002
Study Completion Date:	April 2009
Primary Completion Date:	December 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: EPOCH-Rituximab Addition of monoclonal antibody therapy to chemotherapy for treatment of pts with aggressive CD20+ NHL	Biological: filgrastim Cycle 1: 300 ug (BW < = 70 kg) or 480ug (BW >70 kg) sub Q injection Day 6 until ANC > 5000/uL after nadir counts Subsequent cycle dosages based on previous cycle toxicity or Day 1 Tx toxicity Other Name: G-CSF Biological: rituximab 375 mg/sq m IV infusion Day 1 Cycle 1 Subsequent cycle dosage based on previous cycle or day 1 of tx toxicities Drug: cyclophosphamide 750 mg/sq m IV infusion on Day 5 Cycle 1 Subsequent cycle dosage based on previous cycle or day 1 treatment toxicities Drug: doxorubicin hydrochloride 10 mg/sq m/day continuous IV infusion on Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and Day 1 treatment toxicities Drug: etoposide 50 mg/sq m/day continuous IV infusion Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and day 1 of treatment toxicities Drug: prednisone 60 mg/sq m PO bid days 1-5 of ea cycle Drug: vincristine sulfate 0.4 mg/sq m/day continuous IV infusion uncapped on Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and day 1 of treatment toxicities

Arms

Assigned Interventions

Experimental: EPOCH-Rituximab

Addition of monoclonal antibody therapy to chemotherapy for treatment of pts with aggressive CD20+ NHL

Biological: filgrastim

Cycle 1: 300 ug (BW < = 70 kg) or 480ug (BW >70 kg) sub Q injection Day 6 until ANC > 5000/uL after nadir counts Subsequent cycle dosages based on previous cycle toxicity or Day 1 Tx toxicity

Other Name: G-CSF

Biological: rituximab

375 mg/sq m IV infusion Day 1 Cycle 1 Subsequent cycle dosage based on previous cycle or day 1 of tx toxicities

Drug: cyclophosphamide

750 mg/sq m IV infusion on Day 5 Cycle 1 Subsequent cycle dosage based on previous cycle or day 1 treatment toxicities

Drug: doxorubicin hydrochloride

10 mg/sq m/day continuous IV infusion on Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and Day 1 treatment toxicities

Drug: etoposide

50 mg/sq m/day continuous IV infusion Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and day 1 of treatment toxicities

Drug: prednisone

60 mg/sq m PO bid days 1-5 of ea cycle

Drug: vincristine sulfate

0.4 mg/sq m/day continuous IV infusion uncapped on Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and day 1 of treatment toxicities

Detailed Description:

OBJECTIVES:

Determine the response rate, progression-free survival, and overall survival of patients with previously untreated aggressive CD20+ B-cell diffuse large cell or immunoblastic large cell lymphoma treated with rituximab, doxorubicin, etoposide, vincristine, prednisone, and cyclophosphamide.
Determine the toxic effects of this regimen in these patients.
Correlate tumor proliferation rate (MIB-1), bcl-2 expression, and p53 overexpression with complete response rate, progression-free survival, and overall survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on day 1; doxorubicin IV continuously, etoposide IV continuously, and vincristine IV continuously on days 1-4; oral prednisone twice daily on days 1-5; and cyclophosphamide IV on day 5. Patients also receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients with complete or partial response receive 2 additional courses.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 1 year.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed stage II, III, or IV diffuse large cell lymphoma and WHO variants
- CD20+ large B-cell lymphoma, including those with immunoblastic features
- CD20+ thymic B-cell lymphoma
- No evidence of indolent lymphoma
- No mantle cell lymphomas or equivocal B-cell lymphomas that express markers of mantle cell lymphoma (e.g., cyclin D) or other subtypes
No known lymphomatous involvement of the CNS, including the parenchyma or leptomeninges

PATIENT CHARACTERISTICS:

Age:

Not specified

Performance status:

CALGB 0-2

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 1,000/mm3*
Platelet count at least 100,000/mm3* NOTE: * Unless due to lymphoma

Hepatic:

Bilirubin no greater than 2.0 mg/dL* NOTE: * Unless due to lymphoma or Gilbert's disease

Renal:

Creatinine no greater than 1.5 mg/dL* NOTE: * Unless due to lymphoma

Cardiovascular:

LVEF greater than 45%
No ischemic heart disease
No myocardial infarction or congestive heart failure within the past year

Other:

HIV negative
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior cytotoxic chemotherapy
No other concurrent chemotherapy

Endocrine therapy:

Prior short-course of glucocorticoids allowed
No concurrent hormones except for non-disease-related conditions (e.g., insulin for diabetes)
No concurrent steroids except for adrenal failure
No concurrent dexamethasone or other steroidal antiemetics

Radiotherapy:

Prior limited-field radiotherapy allowed

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00032019

Show 81 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)

More Information

Additional Information:

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

Publications:

Hsi ED, Said J, Johnson JL, et al.: Biologic prognostic markers in diffuse large B-cell lymphoma patients treated with dose adjusted EPOCH-R: a CALGB 50103 correlative science study. [Abstract] Blood 112 (11): A-476, 2008.

Wilson WH, Porcu P, Hurd D, et al.: Phase II study of dose-adjusted EPOCH-R in untreated de novo CD20+ diffuse large B-cell lymphoma (DLBCL)-CALGB 50103. [Abstract] J Clin Oncol 23 (Suppl 16): A-6530, 567s, 2005.

Responsible Party:	Monica M Bertagnolli, MD, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00032019 History of Changes
Other Study ID Numbers:	CDR0000069249, U10CA031946, CALGB-50103
Study First Received:	March 8, 2002
Last Updated:	April 1, 2011
Health Authority:	United States: Federal Government

Keywords provided by Cancer and Leukemia Group B:

stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma

contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Cyclophosphamide
Lenograstim
Rituximab
Doxorubicin

Etoposide
Prednisone
Vincristine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
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 09, 2012