Combination Chemotherapy and Rituximab in Treating Patients With HIV-Associated Stage I, Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma - Full Text View

Sponsor:	AIDS Associated Malignancies Clinical Trials Consortium
Collaborators:	National Cancer Institute (NCI) Eastern Cooperative Oncology Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00049036

Purpose

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

PURPOSE: This randomized phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with HIV-associated stage I, stage II, stage III, or stage IV non-Hodgkin's lymphoma.

Condition	Intervention	Phase
Lymphoma	Biological: rituximab	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
Official Title:	A Randomized Phase II Trial Of EPOCH Given Either Concurrently Or Sequentially With Rituximab In Patients With Intermediate Or High-Grade HIV-Associated B-Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: AIDS Cancer Lymphoma

Drug Information available for: Rituximab

U.S. FDA Resources

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

Primary Outcome Measures:

Complete response as measured by tumor response after completion of study treatment [ Designated as safety issue: No ]

Estimated Enrollment:	70
Study Start Date:	January 2003
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive rituximab IV over 2-4 hours prior to each course of chemotherapy. Treatment repeats every 3 weeks for 4-6 courses. Patients who achieve a complete response after 4 courses of chemotherapy and rituximab receive additional rituximab alone weekly for 2 weeks.	Biological: rituximab Given concurrently or sequentially with combination chemotherapy
Arm II: Experimental Patients do not receive rituximab concurrently with chemotherapy. Beginning 4 weeks after completion of chemotherapy, patients receive rituximab IV over 2-4 hours weekly for 6 weeks.	Biological: rituximab Given concurrently or sequentially with combination chemotherapy

Detailed Description:

OBJECTIVES:

Compare the complete response rate of patients with intermediate- or high-grade HIV-associated stage I, I_E, II, III, or IV B-cell non-Hodgkin's lymphoma treated with etoposide, doxorubicin, vincristine, prednisone, and cyclophosphamide with concurrent versus sequential rituximab.
Compare the toxicity of these regimens in these patients.
Compare time to progression and overall survival of patients treated with these regimens.
Compare the effect of these regimens on immune function (CD4 and CD8 lymphocyte count) in these patients.
Compare the effect of these regimens on HIV and Epstein-Barr virus (EBV) viral load in these patients.
Determine the relationship between EBV viral load and EBV CD8 cytotoxic T cells in the peripheral blood and the presence of EBV in lymphoma tumor cells in patients treated with these regimens.
Determine whether rituximab or the concurrent use of antiretroviral therapy significantly alters the steady state concentration of etoposide, doxorubicin, or vincristine in these patients.
Determine whether steady state concentrations of etoposide and doxorubicin correlate with nadir neutrophil and platelet count in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to CD4 count (less than 100/mm^3 vs at least 100/mm^3), age-adjusted International Prognostic Index adverse risk factors (0 or 1 vs 2 or 3), and concurrent antiretroviral therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive rituximab IV over 2-4 hours prior to each course of chemotherapy. Treatment repeats every 3 weeks for 4-6 courses. Patients who achieve a complete response after 4 courses of chemotherapy and rituximab receive additional rituximab alone weekly for 2 weeks.
Arm II: Patients do not receive rituximab concurrently with chemotherapy. Beginning 4 weeks after completion of chemotherapy, patients receive rituximab IV over 2-4 hours weekly for 6 weeks.

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

PROJECTED ACCRUAL: A total of 70 patients (35 per treatment arm) will be accrued for this study within 1 year.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Documented HIV infection by serologic, culture, or quantitative assays
Histologically or cytologically confirmed B-cell non-Hodgkin's lymphoma (NHL) of any of the following histological subtypes:
- Diffuse large B-cell lymphoma
- High-grade immunoblastic large cell lymphoma
- Anaplastic large cell lymphoma
- Burkitt's lymphoma
- High-grade B-cell lymphoma
- Burkitt-like (small noncleaved cell) lymphoma
Stage I, I_E, II, III, or IV disease
Previously untreated
CD20-positive disease
Measurable or evaluable disease
No primary CNS lymphoma (parenchymal brain or spinal cord tumor)
- Patients with lymphamatous meningitis (positive CSF cytology) are eligible 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 terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 50-100% OR
ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,000/mm^3*
Platelet count ≥ 75,000/mm^3* NOTE: * Unless secondary to lymphoma

Hepatic

Bilirubin < 2.0 mg/dL*
AST/ALT ≤ 5 times upper limit of normal* NOTE: * Unless secondary to hepatic infiltration with lymphoma or isolated hyperbilirubinemia associated with the use of indinavir or other antiretrovirals

Renal

Creatinine < 2.0 mg/dL (unless due to lymphoma)

Cardiovascular

LVEF normal by nuclear scan or echocardiogram

Other

Concurrent Mycobacterium avium infection allowed
No acute active HIV-associated opportunistic infection requiring antibiotics
No other concurrent malignancy except carcinoma in situ of the cervix, nonmetastatic nonmelanoma skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 24 hours since prior colony-stimulating factors
No prior rituximab for intermediate- or high-grade lymphoma
More than 12 months since prior rituximab for other indications (e.g., low-grade lymphoma or idiopathic thrombocytopenic purpura)
Concurrent filgrastim (G-CSF) or epoetin alfa allowed

Chemotherapy

No prior chemotherapy for NHL

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy for NHL

Surgery

Not specified

Other

Concurrent chronic therapy with potentially myelosuppressive agents allowed provided entry hematologic criteria are met

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049036

Locations

United States, Florida
Broward General Medical Center Cancer Center
Fort Lauderdale, Florida, United States, 33316

Sponsors and Collaborators

AIDS Associated Malignancies Clinical Trials Consortium

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Investigators

Investigator:	Lawrence D. Kaplan, MD	San Francisco General Hospital Medical Center
Study Chair:	Joseph A. Sparano, MD	Albert Einstein College of Medicine of Yeshiva University
Study Chair:	Yelena Novik, MD	New York University School of Medicine

More Information

Additional Information:

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

Publications:

Sparano JA, Lee J, Kaplan LD: Randomized phase II trial of infusional EPOCH chemotherapy given either concurrently with or sequentially followed by rituximab in HIV-associated lymphoma: AIDS Malignancy Consortium 034. [Abstract] 10th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies, October 16-17, 2006, Bethesda, MD A-11, 2006.

Chadburn A, Chen X, Chiu A, et al.: Neither germinal center (GC) vs non-germinal center (Non-GC) phenotype nor FOXP1 expression correlate with outcome in AIDS-associated diffuse large B-cell lymphoma (DLBCL): study of patients from AIDS Malignancies Consortium trials 010 and 034. [Abstract] Blood 108 (11): A-2023, 2006.

Responsible Party:	AIDS Associated Malignancies Clinical Trials Consortium ( Jeanette Y. Lee )
Study ID Numbers:	CDR0000257660, AMC-034, ECOG-AMC34
Study First Received:	November 12, 2002
Last Updated:	May 20, 2009
ClinicalTrials.gov Identifier:	NCT00049036 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

AIDS-related diffuse large cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related small noncleaved cell lymphoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Rituximab
Physiological Effects of Drugs
Pharmacologic Actions

Lymphatic Diseases
Neoplasms
Therapeutic Uses
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Antirheumatic Agents
Lymphoma

ClinicalTrials.gov processed this record on November 09, 2009