Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	AMC-034 ECOG-AMC34, NCT00049036

Objectives

1. 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.
2. Compare the toxicity of these regimens in these patients.
3. Compare time to progression and overall survival of patients treated with these regimens.
4. Compare the effect of these regimens on immune function (CD4 and CD8 lymphocyte count) in these patients.
5. Compare the effect of these regimens on HIV and Epstein-Barr virus (EBV) viral load in these patients.
6. 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.
7. Determine whether rituximab or the concurrent use of antiretroviral therapy significantly alters the steady state concentration of etoposide, doxorubicin, or vincristine in these patients.
8. Determine whether steady state concentrations of etoposide and doxorubicin correlate with nadir neutrophil and platelet count in these patients.

Entry 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.]

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

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/mm³*
• Platelet count ≥ 75,000/mm³*

 [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

Expected Enrollment

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

Outcomes

Complete response as measured by tumor response after completion of study treatment

Outline

This is a randomized, open-label, multicenter study. Patients are stratified according to CD4 count (less than 100/mm³ vs at least 100/mm³), 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.

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.

Trial Contact Information

Trial Lead Organizations

AIDS Associated Malignancies Clinical Trials Consortium

Lawrence Kaplan, MD, Protocol co-chair		Ph: 415-206-8000
Joseph Sparano, MD, Protocol chair		Ph: 718-904-2555 Email: jsparano@montefiore.org

Eastern Cooperative Oncology Group

Yelena Novik, MD, Protocol chair		Ph: 212-731-5350 Email: yelena.novik@med.nyu.edu

Registry Information
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
Trial Start Date		2003-01-22
Trial Completion Date		2009-05-13
Registered in ClinicalTrials.gov		NCT00049036
Date Submitted to PDQ		2002-08-30
Information Last Verified		2008-11-25
NCI Grant/Contract Number		CA70019

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