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

Lymphoma Clinical Trial

Official title:

Randomized Trial of CHOP Chemotherapy With or Without Rituximab (Chimeric Anti-CD20 Antibody) for HIV-Associated Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003595
• Other study ID #: NCI-2012-02279
• Secondary ID: AMC-010CPMC-IRB-
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: February 7, 2013
• Start date: January 1999

Study information

• Verified date: May 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. primary completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• filgrastim

• rituximab

Drug:
• CHOP regimen

• cyclophosphamide

• doxorubicin hydrochloride

• prednisone

• vincristine sulfate

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Herbert Irving 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	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	University Hospital/New Jersey Cancer Center	Newark	New Jersey
United States	San Francisco General Hospital Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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.

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 o

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: AI — View Citation