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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003595
First received: November 1, 1999
Last updated: February 7, 2013
Last verified: May 2007
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: CHOP regimen
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Trial of CHOP Chemotherapy With or Without Rituximab (Chimeric Anti-CD20 Antibody) for HIV-Associated Non-Hodgkin's Lymphoma

Resource links provided by NLM:


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

Enrollment: 120
Study Start Date: January 1999
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: filgrastim Biological: rituximab Drug: CHOP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate
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.
Biological: filgrastim Drug: CHOP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003595

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

Additional Information:
Publications:
Chen X, Cesarman E, Hyjek E, et al.: FOXP1 expression in AIDS-associated diffuse large B-cell lymphoma (DLBCL): correlation with prognostic parameters in patients from AIDS Malignancies Consortium Trial 010. [Abstract] United States and Canadian Academy of Pathology 95th Annual Meeting, February 11-17, 2006, Atlanta, GA. A-1016, 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: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003595     History of Changes
Other Study ID Numbers: NCI-2012-02279, AMC-010, CPMC-IRB-9691, CWRU-AMC-1400, UCLA-9810029, CDR0000066666
Study First Received: November 1, 1999
Last Updated: February 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
childhood Burkitt lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related diffuse large cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related small noncleaved cell lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 22, 2014