This study will evaluate the safety and effectiveness of a short course of chemotherapy to treat non-Hodgkin's lymphoma in patients with HIV infection. HIV-infected patients have a weakened immune system and chemotherapy, which is used to treat lymphoma, further compromises immune function. This study will test whether reducing the total amount of chemotherapy using a specific combination of drugs will rid the body of lymphoma quickly, while decreasing the risk of infections and future cancers.

Patients with non-Hodgkin's lymphoma and HIV infection age 4 years and older who are not pregnant or nursing and who have not been treated previously with rituximab may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood and urine tests, and an electrocardiogram. Bone marrow aspiration and biopsy, lumbar puncture (spinal tap), and imaging tests such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET) and x-rays will also be done to determine the location and extent of the lymphoma.

Participants will receive chemotherapy on an outpatient basis for a period of 9 to 18 weeks in 3-week cycles as follows: prednisone by mouth on days 1 through 5; etoposide, doxorubicin and vincristine intravenously (through a vein) on days 1 through 4; and cyclophosphamide by intravenous injection on day 5. In addition, an antibody called rituximab, which attaches to lymphoma cells and may increase the effectiveness of the chemotherapy, will be given twice during each treatment cycle on days 1 and 5. Starting day 6, patients receive no chemotherapy for 16 days. They will, however, receive a drug called G-CSF for about 2 weeks, beginning day 6 of the cycle. G-CSF is a protein naturally produced by bone marrow that may boost immune function. The chemotherapy and rituximab are infused through a vein by means of a lightweight portable pump. Patients are taught how to use this pump, as well as how to give themselves G-CSF injections under the skin. Patients will also receive prophylactic methotrexate via lumbar puncture on cycles 3-5.

Patients with disease in their central nervous system will receive additional chemotherapy (methotrexate, hydrocortisone and cytarabine) via lumbar puncture or an Ommaya-a device that is surgically placed in the head. This is necessary in order to treat lymphoma in the brain and spinal fluid-areas that intravenous drugs cannot reach. For the lumbar puncture, a small needle is inserted through the skin and muscle in the lower back, going between the bones of the spine until the needle punctures the spinal canal covering. If lumbar puncture is not feasible, an Ommaya may be used.

If evidence of lymphoma disappears quickly, treatment will be stopped after 3 cycles. In any case, patients will receive a maximum of 6 cycles. They will be followed periodically for 2 years with various tests, such as blood tests and imaging scans, to monitor disease progress.

Condition	Treatment or Intervention	Phase
AIDS Related Lymphoma HIV Infection	Drug: Rituximab	Phase II

Further Study Details: 

Expected Total Enrollment:  28

This is a study to investigate in a preliminary fashion the feasibility of short course chemotherapy to patients with HIV-associated non-Hodgkin's lymphoma (HIV-NHL). Patients will be treated every three weeks with a combination of EPOCH and rituximab for one cycle beyond complete resolution by CAT scan of all detectable tumors for a minimum of three and maximum of six cycles. Restaging of disease sites by computed axial tomography (CAT) scans will be performed after each cycle of therapy. Following cycle 3, CAT, positron emission tomography scans (PET), and bone marrow biopsies (if initially positive) will be performed. This study will investigate if the paradigm for treatment can be successfully changed from a standard of 6 cycles to one cycle beyond complete remission with 6 total allowable cycles. At the conclusion of the study, we will estimate whether the number of cycles can be reduced using the paradigm. If the cumulative number of patients to relapse exceeds 25 percent by 6 months, the study will be closed. Following the completion of chemotherapy, restaging will be performed 2 months following the end of treatment,

then every 3 months for one year, every 6 months for one year, then every 12 months

until relapse. death, or loss to follow up.

Anti-HIV therapy will be suspended prior to initiation of the chemotherapy and optimum therapy will be reinitiated after all the cycles have been administered. To study the effects of treatment approach on parameters of HIV disease, measurements of CD4 cells and viral loads will be made at baseline and at the completion of therapy, and then 2 months following the end of treatment, and then every 3-6 months for a total of 24 months following chemotherapy.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Aggressive CD20 positive NHL confirmed by Pathology, DCS.
HIV + serology.
All stages (I-IV) of disease.
ECOG Performance status 0-4
NHL previously untreated with cytotoxic chemotherapy.
Age greater than or equal to 4 years
Laboratory tests (unless impairment due to respective organ involvement by tumor):
-Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than or equal to 50 ml/min
Pediatric patients: Age-adjusted normal serum creatinine according to the following table or a creatinine clearance greater than 60 ml/min/1.73 m(2).
Less than or equal to 5 age (years), 0.8 Maximum serum creatinine
Greater than 5, less than or equal to 10 age (years), 1.0 Maximum serum creatinine
Greater than 10, less than or equal to 15 age (years), 1.2 Maximum serum creatinine
Greater than 15 age (years), 1.5 Maximum serum creatinine
-Bilirubin less than 2.0 mg/dl, or total bilirubin less than or equal to 4.5 mg/dl with direct fraction less than or equal to 0.3 mg/dl in patients for whom these abnormalities are felt to be due to protease inhibitor therapy
-AST and ALT less than or equal to 3x ULN (AST and ALT less than or equal to 6x ULN for patients on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation)
-ANC greater than or equal to 1000/mm(3)
-Platelet greater than or equal to 75,000/mm(3) (unless impairment due to ITP)
Ability of patient or parent/guardian to provide informed consent.
EXCLUSION CRITERIA:
Previous rituximab
Pregnancy or nursing.
- Doxorubicin, etoposide, vincristine and cyclophosphamide are teratogenic and may be excreted in milk.
- Antiretroviral therapy is indicated during pregnancy and nursing.
Current clinical heart failure or symptomatic ischemic heart disease.
Serious underlying medical condition or infection other than HIV that would contraindicate SC-EPOCH-R.
- Examples include, but are not limited to:

• Severe AIDS-related wasting

• Sever intractable diarrhea

• Active inadequately treated opportunistic infection of the CNS

Concurrent anti-retroviral therapy during EPOCH therapy.
Primary CNS lymphoma.
Adolescents who do not freely assent

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  010030; 01-C-0030
Record last reviewed:  August 1, 2004
Last Updated:  January 14, 2005
Record first received:  November 3, 2000
ClinicalTrials.gov Identifier:  NCT00006436
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08