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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00003595

Collaborator

(none)

120

Enrollment

Locations

Arms

9.2

Patients Per Site

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: filgrastim Biological: rituximab Drug: CHOP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate	Phase 3

Detailed Description

OBJECTIVES:

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.
Determine the efficacy of rituximab as maintenance therapy following remission induction with CHOP in these patients.
Determine the effect of rituximab on the immune system and HIV viral load in these patients.
Determine the relationship between EBV load and the presence of EBV in lymphoma tumor cells of these patients.
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 Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Jan 1, 1999

Actual Primary Completion Date :

Apr 1, 2006

Arms and Interventions

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.	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

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.

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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