Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Closed	18 and over	NCI	AMC-047 AMC-047, NCT00389818

Objectives

Primary

1. 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).
2. Determine the duration of response (relapse-free survival) in patients treated with this regimen.
3. Determine the median survival time of patients treated with this regimen.
4. Determine rate of bacterial, fungal, and opportunistic infections in patients treated with this regimen.

Secondary

1. Determine, preliminarily, the relationship between MDR-1 expression in tumor tissue and response to therapy in patients treated with this regimen.
2. Determine, preliminarily, any relationship between response and survival and BCL-2 expression in tumor tissue in patients treated with this regimen.
3. 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.
4. Compare the results of positron emission tomography (PET) scanning with traditional CT scans in predicting response to therapy in these patients.
5. Examine the relationship between chemotherapeutic drug levels and receipt of specific antiretroviral and/or anti-infective medications in these patients.
6. Examine the mortality and the causes of death in patients treated with this regimen.
7. Determine event-free survival at 1 year.

Entry 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

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

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 PO₂ ≥ 70 or pulse oximeter-derived O₂ saturation ≥ 94% on room air (unless due to lymphomatous involvement of the lungs)
• Able to comply with study and provide adequate informed consent

Expected Enrollment

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

Outcomes

Complete response rate (complete response and complete response unconfirmed)
Duration of response
Median survival time
Rate of bacterial, fungal, and opportunistic infections

Relationship between MDR-1 expression and response to treatment
Relationship between response and survival and BCL-2 expression in tumor tissue
Relationship between development of bacterial, fungal, and/or opportunistic infections and baseline CD4 lymphocyte count, HIV-1 RNA level, and quantitative immunoglobin level, or changes in quantitative immunoglobin levels over time
Mortality and cause of death
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.

Trial Contact Information

Trial Lead Organizations

AIDS Associated Malignancies Clinical Trials Consortium

Alexandra Levine, MD, Protocol chair		Ph: 626-471-7213; 800-826-4673

Registry Information
Official Title		A Phase II Trial of Doxil, Rituximab, Cyclophosphamide, Vincristine, and Prednisone (DR-COP) in Patients with Newly Diagnosed AIDS-Associated B-Cell Non-Hodgkin's Lymphoma
Trial Start Date		2007-01-31
Trial Completion Date		2009-08-03 (estimated)
Registered in ClinicalTrials.gov		NCT00389818
Date Submitted to PDQ		2006-08-30
Information Last Verified		2009-09-16
NCI Grant/Contract Number		CA70019

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