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

November 1, 1999
February 7, 2013
January 1999
April 2006   (final data collection date for primary outcome measure)
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Not Provided
Complete list of historical versions of study NCT00003595 on ClinicalTrials.gov Archive Site
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Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With Previously Untreated HIV-Associated Non-Hodgkin's Lymphoma
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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • Biological: filgrastim
  • Biological: rituximab
  • Drug: CHOP regimen
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: prednisone
  • Drug: vincristine sulfate
  • 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.
    Interventions:
    • 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.
    Interventions:
    • Biological: filgrastim
    • Drug: CHOP regimen
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: prednisone
    • Drug: vincristine sulfate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
120
Not Provided
April 2006   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00003595
NCI-2012-02279, AMC-010, CPMC-IRB-9691, CWRU-AMC-1400, UCLA-9810029, CDR0000066666
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Study Chair: Lawrence D. Kaplan, MD University of California, San Francisco
National Cancer Institute (NCI)
May 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP