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 Active 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 every 2 months for 1 year and then every 6 months for 2 years.

Trial Contact Information

Trial Lead Organizations

AIDS Associated Malignancies Clinical Trials Consortium

Alexandra Levine, MD, Protocol chair		Ph: 323-865-3913; 800-865-0102

U.S.A.
California
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
	Los Angeles
	UCLA Clinical AIDS Research and Education (CARE) Center
		Ronald Mitsuyasu, MD	Ph:  310-557-1891
			Email: rmitsuya@mednet.ucla.edu
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
Florida
	Miami
	University of Miami Sylvester Comprehensive Cancer Center - Miami
		University of Miami Sylvester Comprehensive Cancer Center Clinical Trial Matching Service	Ph:  866-574-5124
			Email: Sylvester@emergingmed.com
Illinois
	Chicago
	Robert H. Lurie Comprehensive Cancer Center at Northwestern University
		Clinical Trials Office - Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Ph:  312-695-1301
			Email: cancer@northwestern.edu
Massachusetts
	Boston
	Beth Israel Deaconess Medical Center
		Clinical Trials Office - Beth Israel Deaconess Medical Center	Ph:  617-667-9925
Missouri
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Lee Ratner, MD, PhD	Ph:  314-362-8836 800-600-3606
			Email: lratner@im.wustl.edu
New York
	Bronx
	Albert Einstein Cancer Center at Albert Einstein College of Medicine
		Clinical Trials Office - Albert Einstein Cancer Center at Albert Einstein College of Medicine	Ph:  718-904-2730
			Email: aecc@aecom.yu.edu
	New York
	Memorial Sloan-Kettering Cancer Center
		Susan Krown, MD	Ph:  212-639-7426 800-525-2225
			Email: krowns@mskcc.org
Pennsylvania
	Philadelphia
	Joan Karnell Cancer Center at Pennsylvania Hospital
		David Henry, MD	Ph:  215-829-6088
			Email: dhhenry@juno.com

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		2008-03-26 (estimated)
Registered in ClinicalTrials.gov		NCT00389818
Date Submitted to PDQ		2006-08-30
Information Last Verified		2008-04-20
NCI Grant/Contract Number		CA70019

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