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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 3

Conditions: Lymphoma

Treatments: Drug: prednisone; Biological: filgrastim; Drug: doxorubicin hydrochloride; Biological: rituximab; Drug: vincristine sulfate; Drug: CHOP regimen; Drug: cyclophosphamide

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003595

AMC-010

CPMC-IRB-9691

UCLA-9810029

NCI-2012-02279

CWRU-AMC-1400

CDR0000066666 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Arm I

Experimental group

Description:

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.

Treatment:

Biological: rituximab

Drug: prednisone

Biological: filgrastim

Drug: CHOP regimen

Drug: vincristine sulfate

Drug: doxorubicin hydrochloride

Drug: cyclophosphamide

Arm II

Active Comparator group

Description:

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.

Treatment:

Drug: prednisone

Biological: filgrastim

Drug: CHOP regimen

Drug: vincristine sulfate

Drug: doxorubicin hydrochloride

Drug: cyclophosphamide