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

NCT ID: NCT00003595

Last Updated: 2013-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-01-31

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.

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.

Conditions

Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

CHOP regimen

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

filgrastim

Intervention Type: BIOLOGICAL

CHOP regimen

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

Interventions

filgrastim

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

CHOP regimen

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lawrence D. Kaplan, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

San Francisco General Hospital Medical Center

San Francisco, California, United States

Sylvester Cancer Center, University of Miami

Miami, Florida, United States

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University Hospital/New Jersey Cancer Center

Newark, New Jersey, United States

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Mount Sinai School of Medicine

New York, New York, United States

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Ireland Cancer Center

Cleveland, Ohio, United States

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

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.

Reference Type: RESULT

Kaplan LD, Lee JY, Ambinder RF, Sparano JA, Cesarman E, Chadburn A, Levine AM, Scadden DT. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood. 2005 Sep 1;106(5):1538-43. doi: 10.1182/blood-2005-04-1437. Epub 2005 May 24.

Reference Type: RESULT

PMID: 15914552 (View on PubMed)

Other Identifiers

AMC-010

Identifier Type: -

Identifier Source: secondary_id

CPMC-IRB-9691

Identifier Type: -

Identifier Source: secondary_id

CWRU-AMC-1400

Identifier Type: -

Identifier Source: secondary_id

UCLA-9810029

Identifier Type: -

Identifier Source: secondary_id

CDR0000066666

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02279

Identifier Type: -

Identifier Source: org_study_id