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

April 28, 2014 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

106

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Rockville, Maryland, United States, 20850
        • AIDS - Associated Malignancies Clinical Trials Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: laboratory biomarker analysis
Correlative studies
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • Adriamycin PFS
  • Adriamycin RDF
  • ADR
  • Adria
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • leurocristine sulfate
  • Vincasar PFS
Drug: prednisone
Given orally
Other Names:
  • DeCortin
  • Deltra
Experimental: 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.
Other: laboratory biomarker analysis
Correlative studies
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • Adriamycin PFS
  • Adriamycin RDF
  • ADR
  • Adria
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • leurocristine sulfate
  • Vincasar PFS
Drug: prednisone
Given orally
Other Names:
  • DeCortin
  • Deltra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response Proportion as Measured by Tumor Response After Completion of Study Treatment
Time Frame: 60 days
Complete response defined by the International Response Criteria for Non-Hodgkin's Lymphoma
60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Joseph Sparano, AIDS Associated Malignancies Clinical Trials Consortium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2003

Primary Completion (Actual)

May 1, 2009

Study Completion (Actual)

May 1, 2009

Study Registration Dates

First Submitted

November 12, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

May 14, 2014

Last Update Submitted That Met QC Criteria

April 28, 2014

Last Verified

December 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02926 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U01CA070019 (U.S. NIH Grant/Contract)
  • ECOG-AMC34
  • CDR0000257660
  • AMC-034 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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