Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With Previously Untreated HIV-Associated Non-Hodgkin's Lymphoma

February 7, 2013 updated by: National Cancer Institute (NCI)

Randomized Trial of CHOP Chemotherapy With or Without Rituximab (Chimeric Anti-CD20 Antibody) for HIV-Associated Non-Hodgkin's Lymphoma

Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without monoclonal antibody therapy in treating patients who have previously untreated HIV-associated non-Hodgkin's lymphoma. 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 cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy plus monoclonal antibody therapy is more effective than combination chemotherapy alone in treating HIV-associated non-Hodgkin's lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. Compare the efficacy of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab in patients with previously untreated HIV-associated non-Hodgkin's lymphoma.

II. Determine the efficacy of rituximab as maintenance therapy following remission induction with CHOP in these patients.

III. Determine the effect of rituximab on the immune system and HIV viral load in these patients.

IV. Determine the relationship between EBV load and the presence of EBV in lymphoma tumor cells of these patients.

V. Compare the effect of CHOP with or without rituximab on EBV load in these patients.

OUTLINE: This is a randomized, multicenter study.

Patients are stratified by extent of disease (stage I/II vs III/IV). Patients are randomized to 1 of 2 treatment arms:

Arm I: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 3 and oral prednisone on days 3-7. Patients receive rituximab on day 1. Treatment repeats every 3 weeks for a minimum of 4 courses or 2 courses beyond complete response in the absence of disease progression or unacceptable toxicity. Patients with stage I, stage IE (including bulky), or nonbulky stage II or IIE disease receive 3 courses of chemotherapy with rituximab followed by radiotherapy beginning 3 weeks after completion of the third course. Patients who achieve partial response for a minimum of 28 days or complete response receive maintenance rituximab IV beginning on day 28 of the final course of chemotherapy. Maintenance rituximab treatment repeats every 4 weeks for 3 courses.

Arm II: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 3 weeks for a minimum of 4 courses or 2 courses beyond complete response. Patients with stage I, stage IE (including bulky), or nonbulky stage II or IIE disease receive 3 courses of chemotherapy. Patients receive radiotherapy beginning 3 weeks after completion of the third course of chemotherapy.

Both arms: Patients receive filgrastim (G-CSF) subcutaneously beginning on day 4 and continuing through day 13 of each chemotherapy course or until blood counts recover.

Patients are followed every 4 weeks for 1 year and then every 2 months until death.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 3

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
    • California
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center, UCLA
      • Los Angeles, California, United States, 90033-0804
        • USC/Norris Comprehensive Cancer Center and Hospital
      • San Francisco, California, United States, 94110
        • San Francisco General Hospital Medical Center
    • Florida
      • Miami, Florida, United States, 33136
        • Sylvester Cancer Center, University of Miami
    • Illinois
      • Chicago, Illinois, United States, 60611-3013
        • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
    • Massachusetts
      • Boston, Massachusetts, United States, 02114-2617
        • Massachusetts General Hospital
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • University Hospital/New Jersey Cancer Center
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU School of Medicine's Kaplan Comprehensive Cancer Center
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44106-5065
        • Ireland Cancer Center
      • Columbus, Ohio, United States, 43210-1240
        • Arthur G. James Cancer Hospital - Ohio State University

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically proven HIV-associated B cell non-Hodgkin's lymphoma, including:
  • Diffuse large B cell lymphoma
  • Intermediate grade diffuse large cell lymphoma
  • High grade large cell immunoblastic lymphoma
  • Burkitt's lymphoma
  • High grade B cell lymphoma, Burkitt's like (small noncleaved lymphoma)
  • No primary CNS lymphoma (parenchymal brain or spinal cord tumor)
  • Evaluable disease HIV documentation may be serologic (ELISA or western blot), culture, or quantitative PCR or bDNA assay Tumors must be CD20 positive (greater than 50% cells express CD20)
  • 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 former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

  • Age: Over 18
  • Performance status: Karnofsky 70-100%
  • Absolute neutrophil count greater than 1,000/mm3*

  • Platelet count greater than 75,000/mm3*

    * Unless cytopenias are secondary to lymphoma

  • Bilirubin less than 2.0 mg/dL (unless secondary to hepatic infiltration with lymphoma or isolated hyperbilirubinemia associated with the use of indinavir)
  • SGOT or SGPT less than 7 times upper limit of normal
  • Creatinine less than 2.0 mg/dL (unless due to lymphoma)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No acute, active HIV-associated opportunistic infection requiring antibiotics
  • Mycobacterium avium complex allowed
  • No concurrent malignancy except carcinoma in situ of the cervix, nonmetastatic nonmelanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy

PRIOR CONCURRENT THERAPY:

  • Prior or concurrent epoetin alfa or filgrastim (G-CSF) allowed
  • No prior colony stimulating factor therapy within 24 hours prior to chemotherapy
  • No prior chemotherapy for HIV-associated non-Hodgkin's lymphoma
  • At least 1 year since prior cyclophosphamide or doxorubicin
  • No prior radiotherapy for HIV-associated non-Hodgkin's lymphoma
  • Chronic therapy with myelosuppressive agents allowed
  • Concurrent antiretroviral therapy, antifungal medications, and antibiotics allowed

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 cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 3 and oral prednisone on days 3-7. Patients receive rituximab on day 1. Treatment repeats every 3 weeks for a minimum of 4 courses or 2 courses beyond complete response in the absence of disease progression or unacceptable toxicity. Patients with stage I, stage IE (including bulky), or nonbulky stage II or IIE disease receive 3 courses of chemotherapy with rituximab followed by radiotherapy beginning 3 weeks after completion of the third course. Patients who achieve partial response for a minimum of 28 days or complete response receive maintenance rituximab IV beginning on day 28 of the final course of chemotherapy. Maintenance rituximab treatment repeats every 4 weeks for 3 courses.
Drug: cyclophosphamide
Drug: prednisone
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Biological: filgrastim
Biological: rituximab
Drug: CHOP regimen
Active Comparator: Arm II
Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 3 weeks for a minimum of 4 courses or 2 courses beyond complete response. Patients with stage I, stage IE (including bulky), or nonbulky stage II or IIE disease receive 3 courses of chemotherapy. Patients receive radiotherapy beginning 3 weeks after completion of the third course of chemotherapy.
Drug: cyclophosphamide
Drug: prednisone
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Biological: filgrastim
Drug: CHOP regimen

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

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

January 1, 1999

Primary Completion (Actual)

April 1, 2006

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

October 27, 2003

First Posted (Estimate)

October 28, 2003

Study Record Updates

Last Update Posted (Estimate)

February 8, 2013

Last Update Submitted That Met QC Criteria

February 7, 2013

Last Verified

May 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02279
  • AMC-010
  • CPMC-IRB-9691
  • CWRU-AMC-1400
  • UCLA-9810029
  • CDR0000066666 (Registry Identifier: PDQ (Physician Data Query))

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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