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

NCT ID: NCT00049036

Last Updated: 2014-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-03-31
• Study Completion Date: 2009-05-31

Brief Summary

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. 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.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the complete response rate after treatment with EPOCH given either concurrently or sequentially with rituximab.

SECONDARY OBJECTIVES:

I. To evaluate the toxicity of EPOCH given either concurrently or sequentially with rituximab.

II. To evaluate the effect of EPOCH given either concurrently or sequentially with rituximab on immune function (CD4, CD8 lymphocyte count) after two cycles of EPOCH, and 1 month, 3 months, 6 months, and 12 months after the completion of EPOCH.

III. To evaluate the effect of EPOCH given either concurrently or sequentially with rituximab on HIV and EBV viral load after two cycles of EPOCH, and 1 month, 3 months, 6 months, and 12 months after the completion of EPOCH.

IV. To evaluate 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.

V. To determine whether rituximab or the concurrent use of antiretroviral therapy significantly alters the steady state concentration of etoposide, doxorubicin, or vincristine during the first cycle of therapy.

VI. To determine whether steady state concentration of etoposide or doxorubicin correlate with nadir neutrophil and platelet count during the first cycle of therapy.

VII. To determine time to progression and overall survival in patients treated with EPOCH given either concurrently or sequentially with rituximab.

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 intravenously (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.

Conditions

AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive rituximab intravenously (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.

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

Given IV

etoposide

Intervention Type: DRUG

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

vincristine sulfate

Intervention Type: DRUG

Given IV

prednisone

Intervention Type: DRUG

Given orally

cyclophosphamide

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

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.

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

Given IV

etoposide

Intervention Type: DRUG

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

vincristine sulfate

Intervention Type: DRUG

Given IV

prednisone

Intervention Type: DRUG

Given orally

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

rituximab

Given IV

Intervention Type: BIOLOGICAL

etoposide

Given IV

Intervention Type: DRUG

doxorubicin hydrochloride

Given IV

Intervention Type: DRUG

vincristine sulfate

Given IV

Intervention Type: DRUG

prednisone

Given orally

Intervention Type: DRUG

cyclophosphamide

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

IDEC-C2B8; IDEC-C2B8 monoclonal antibody; Mabthera; MOAB IDEC-C2B8; Rituxan; EPEG; VP-16; VP-16-213; ADM; ADR; Adria; Adriamycin PFS; Adriamycin RDF; leurocristine sulfate; VCR; Vincasar PFS; DeCortin; Deltra; CPM; CTX; Cytoxan; Endoxan; Endoxana

Eligibility Criteria

Inclusion Criteria

• Previously untreated histologically or cytologically documented B-cell non-Hodgkin's lymphoma; the following histologies are eligible: diffuse large B-cell lymphoma, high-grade large cell immunoblastic lymphoma, anaplastic large cell lymphoma, Burkitt's lymphoma, high-grade B-cell lymphoma, Burkitt-like (small non-cleaved lymphoma)
• Tumors must be CD20 positive
• Documented HIV infection: documentation may be serologic (ELISA, western blot), culture, or quantitative PCR or bDNA assays
• Evaluable or measurable disease
• Stage I and IE or Stage II-IV disease patients
• ANC >= 1000 cells/mm^3
• Platelet count >= 75,000/mm^3 unless cytopenias are secondary to lymphoma
• All patients must be off colony stimulating factor therapy at least 24 hours prior to chemotherapy
• Transaminase =< 5 times the upper limit of normal unless secondary to hepatic infiltration with lymphoma or isolated hyperbilirubinemia associated with the use of indinavir or other antiretrovirals
• Total Bilirubin < 2.0 unless secondary to hepatic infiltration with lymphoma or isolated hyperbilirubinemia associated with the use of indinavir or other antiretrovirals; for bilirubin > 3.0 due to hepatic involvement the initial dose of doxorubicin will be decreased by 50% and the initial dose of vincristine will be omitted
• Creatinine < 2.0 unless due to lymphoma
• KPS >= 50 (ECOG PS 0, 1, or 2)
• Able to give consent
• Female patients must have a negative pregnancy test within 72 hours of entering into the study; males and females must agree to use adequate birth control if conception is possible during the study; women must avoid pregnancy and men avoid fathering children while in the study
• Patients already receiving erythropoeitin or G-CSF are eligible
• Patients must have a left ventricular ejection fraction that is at or above the lower institutional limits of normal, as assessed by nuclear scan or echocardiogram obtained within 12 weeks of registration
• Lymphomatous meningitis (patients with a positive CSF cytology are eligible)

Exclusion Criteria

• Previous chemotherapy or radiotherapy for this lymphoma
• Primary Central Nervous System Lymphoma (parenchymal brain or spinal cord tumor)
• Acute active HIV-associated opportunistic infection requiring antibiotic treatment; patients with mycobacterium avium are not excluded; chronic therapy with potentially myelosuppressive agents is allowed provided that entry hematologic criteria are met
• Concurrent malignancy (excluding in situ cervical cancer, or non-metastatic non-melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy)
• Previous therapy with rituximab within 12 months; patients treated with rituximab more than 12 months earlier are eligible only if it was given for indications other than the treatment of intermediate- or high-grade lymphoma (eg, low-grade lymphoma or ITP)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Sparano

Role: PRINCIPAL_INVESTIGATOR

AIDS Associated Malignancies Clinical Trials Consortium

Locations

AIDS - Associated Malignancies Clinical Trials Consortium

Rockville, Maryland, United States

Countries

United States

References

Sparano JA, Lee JY, Kaplan LD, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R. Response-adapted therapy with infusional EPOCH chemotherapy plus rituximab in HIV-associated, B-cell non-Hodgkin's lymphoma. Haematologica. 2021 Mar 1;106(3):730-735. doi: 10.3324/haematol.2019.243386.

Reference Type: DERIVED

PMID: 32107337 (View on PubMed)

Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R; AIDS Malignancy Consortium. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010 Apr 15;115(15):3008-16. doi: 10.1182/blood-2009-08-231613. Epub 2009 Dec 18.

Reference Type: DERIVED

PMID: 20023215 (View on PubMed)

Other Identifiers

NCI-2012-02926

Identifier Type: REGISTRY

Identifier Source: secondary_id

ECOG-AMC34

Identifier Type: -

Identifier Source: secondary_id

CDR0000257660

Identifier Type: -

Identifier Source: secondary_id

AMC-034

Identifier Type: OTHER

Identifier Source: secondary_id

AMC-034

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA070019

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02926

Identifier Type: -

Identifier Source: org_study_id