Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed AIDS-Related B-Cell Non-Hodgkin's Lymphoma

AIDS Malignancy Consortium

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Biological: pegfilgrastim

Biological: filgrastim

Drug: prednisone

Drug: cyclophosphamide

Biological: rituximab

Other: laboratory biomarker analysis

Biological: sargramostim

Drug: vincristine sulfate

Other: immunohistochemistry staining method

Drug: pegylated liposomal doxorubicin hydrochloride

Study type

Interventional

Funder types

NETWORK

Industry

NIH

Identifiers

NCT00389818

AMC-047

U01CA070019 (U.S. NIH Grant/Contract)

CDR0000507634 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving combination chemotherapy together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with newly diagnosed AIDS-related B-cell non-Hodgkin's lymphoma.

Full description

OBJECTIVES:

Primary

Determine the complete response rate (complete response and complete response unconfirmed) in patients with newly diagnosed, AIDS-related B-cell non-Hodgkin's lymphoma treated with doxorubicin hydrochloride liposome, rituximab, cyclophosphamide, vincristine, and prednisone (DR-COP).
Determine the duration of response (relapse-free survival) in patients treated with this regimen.
Determine the median survival time of patients treated with this regimen.
Determine rate of bacterial, fungal, and opportunistic infections in patients treated with this regimen.

Secondary

Determine, preliminarily, the relationship between MDR-1 expression in tumor tissue and response to therapy in patients treated with this regimen.
Determine, preliminarily, any relationship between response and survival and BCL-2 expression in tumor tissue in patients treated with this regimen.
Determine any relationship between development of bacterial, fungal, and/or opportunistic infections and baseline CD4 lymphocyte count, HIV-1 RNA level, and quantitative immunoglobulin levels, or changes in quantitative immunoglobulin levels over time in patients treated with this regimen.
Compare the results of positron emission tomography (PET) scanning with traditional CT scans in predicting response to therapy in these patients.
Examine the relationship between chemotherapeutic drug levels and receipt of specific antiretroviral and/or anti-infective medications in these patients.
Examine the mortality and the causes of death in patients treated with this regimen.
Determine event-free survival at 1 year.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive doxorubicin hydrochloride liposome IV over 90 minutes, rituximab IV over 5-7 hours, cyclophosphamide IV over 1 hour, and vincristine IV over 1-2 minutes on day 1 and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21-28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo laboratory/biomarker studies at baseline and after every 2 courses of chemotherapy. Tissue is examined by immunohistochemistry for BCL-2, Ki67, and MDR-1, along with other markers.

After completion of study treatment, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Enrollment

43 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed AIDS-related B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes:
- Grade III follicular large cell lymphoma
- Diffuse large B-cell lymphoma
- Immunoblastic lymphoma
- Plasmablastic lymphoma
- Primary effusion lymphoma
Previously untreated disease
Any stage disease
CD20 positive disease
Must have documented HIV infection
- Documentation may be by serology (enzyme-linked immunosorbent assay, western blot), culture, or quantitative polymerase chain reaction or branched DNA assays
- Prior documentation of HIV seropositivity allowed
Measurable or nonmeasurable disease
Currently receiving effective highly active anti-retroviral therapy
No primary CNS lymphoma, including parenchymal brain or spinal cord lymphoma
No presence of leptomeningeal disease (positive cerebrospinal fluid for lymphoma) or presence of metastatic disease to brain, in terms of any mass lesion

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100%
Life expectancy ≥ 2 months
Absolute granulocyte (neutrophil) count ≥ 1,000/mm³ (unless secondary to lymphomatous involvement of bone marrow)
Platelet count ≥ 75,000/mm³ (unless secondary to lymphomatous involvement of bone marrow or due to HIV-related thrombocytopenia)
Bilirubin ≤ 2.0 mg/dL (unless elevated secondary to lymphomatous involvement of liver or biliary system or due to other HIV medications [e.g., indinavir, tenofavir, or atazanavir])
SGOT ≤ 5 times upper limit of normal
Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min (unless secondary to renal involvement by lymphoma)
LVEF normal by MUGA or echocardiogram
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after completion of study treatment
No other malignancy, except nonmelanoma skin cancer, carcinoma in situ of the cervix, or Kaposi's sarcoma that does not require systemic therapy
No serious, ongoing, nonmalignant disease or infection that would preclude study compliance, in the opinion of the investigator
No history of cutaneous or mucocutaneous reactions, or diseases in the past, due to any cause, severe enough to cause hospitalization or an inability to eat or drink for ≥ 2 days
No acute, intercurrent infection that would preclude study treatment
- Patients with Mycobacterium avium are eligible
No cardiovascular problems, including any of the following:
- Myocardial infarction within the past 6 months
- New York Heart Association class II-IV heart failure
- Uncontrolled angina
- Severe uncontrolled ventricular arrhythmias
- Clinically significant pericardial disease
- ECG evidence of acute ischemic or active conduction system abnormalities.
No shortness of breath at rest
Arterial PO_2 ≥ 70 or pulse oximeter-derived O_2 saturation ≥ 94% on room air (unless due to lymphomatous involvement of the lungs)
Able to comply with study and provide adequate informed consent

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 4 weeks since prior major surgery (except diagnostic surgery)
At least 12 months since prior rituximab unless it was only given for indications other than the treatment of aggressive lymphoma
No prior cytotoxic chemotherapy or radiotherapy for this lymphoma
- Concurrent radiotherapy, with or without steroids, for emergency conditions secondary to lymphoma (i.e., CNS tumor or cord compression) allowed
No zidovudine or zidovudine-containing regimen (including Combivir® or Trizivir®) during and for 2 months after completion of chemotherapy
Concurrent erythropoietin or filgrastim (G-CSF) allowed
- Growth factor therapy must be discontinued ≥ 24 hours prior to study entry