Randomized Trial of CHOP Chemotherapy With or Without Rituximab (Chimeric Anti-CD20 Antibody) for HIV-Associated Non-Hodgkin's Lymphoma
18 Years
N/A
Both
Lymphoma
Trial Information
Randomized Trial of CHOP Chemotherapy With or Without Rituximab (Chimeric Anti-CD20 Antibody) for 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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Lawrence D. Kaplan, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, San Francisco
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02279
NCT ID:
NCT00003595
Start Date:
January 1999
Completion Date:
Related Keywords:
- Lymphoma
- 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
- Lymphoma
- Lymphoma, Non-Hodgkin
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
| Ireland Cancer Center | Cleveland, Ohio 44106-5065 |
| Arthur G. James Cancer Hospital - Ohio State University | Columbus, Ohio 43210 |
| Robert H. Lurie Comprehensive Cancer Center, Northwestern University | Chicago, Illinois 60611 |
| Sylvester Cancer Center, University of Miami | Miami, Florida 33136 |
| Mount Sinai School of Medicine | New York, New York 10029 |
| NYU School of Medicine's Kaplan Comprehensive Cancer Center | New York, New York 10016 |
| USC/Norris Comprehensive Cancer Center and Hospital | Los Angeles, California 90033-0804 |
| Herbert Irving Comprehensive Cancer Center | New York, New York 10032 |
| San Francisco General Hospital Medical Center | San Francisco, California 94110 |
| Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
| University Hospital/New Jersey Cancer Center | Newark, New Jersey 07103 |
