Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	Over 18	NCI	AMC-010 CPMC-IRB-9691, CWRU-AMC-1400, UCLA-9810029, NCT00003595

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.

Entry 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.

Prior/Concurrent Therapy:

Biologic therapy:
 Prior or concurrent epoetin alfa or filgrastim (G-CSF) allowed
 No prior colony stimulating factor therapy within 24 hours prior to          
  chemotherapy
  
Chemotherapy:
 No prior chemotherapy for HIV-associated non-Hodgkin's lymphoma
 At least 1 year since prior cyclophosphamide or doxorubicin

Endocrine therapy:
 Not specified   

Radiotherapy:
 No prior radiotherapy for HIV-associated non-Hodgkin's lymphoma

Surgery:
 Not specified
 
Other:
 Chronic therapy with myelosuppressive agents allowed
 Concurrent antiretroviral therapy, antifungal medications, and antibiotics
  allowed

Patient Characteristics:

Age:
 Over 18

Performance status:
 Karnofsky 70-100%

Life expectancy:
 Not specified   

Hematopoietic:
 Absolute neutrophil count greater than 1,000/mm3*
 Platelet count greater than 75,000/mm3*
 * Unless cytopenias are secondary to lymphoma
 
Hepatic:
 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

Renal:
 Creatinine less than 2.0 mg/dL (unless due to lymphoma)

Other:
 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

Expected Enrollment

A total of 120 patients will be accrued for this study within 2 years.

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.     

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.

Kaplan LD, Lee JY, Ambinder RF, et al.: 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 106 (5): 1538-43, 2005.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

AIDS Associated Malignancies Clinical Trials Consortium

Lawrence Kaplan, MD, Protocol chair		Ph: 415-353-2661; 800-888-8664 Email: lkaplan@medicine.ucsf.edu

Registry Information
Official Title		Randomized Trial of CHOP Chemotherapy With or Without Rituximab (Chimeric Anti-CD20 Antibody) for HIV-Associated Non-Hodgkin's Lymphoma
Trial Start Date		1999-01-19
Registered in ClinicalTrials.gov		NCT00003595
Date Submitted to PDQ		1998-09-25
Information Last Verified		2007-05-25
NCI Grant/Contract Number		CA70019