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

NCT ID: NCT00389818

Last Updated: 2018-06-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2011-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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DR-COP

Single arm interventional study: all subjects receive DR-COP regimen.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

Supportive therapy: GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

pegfilgrastim

Intervention Type BIOLOGICAL

GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

rituximab

Intervention Type BIOLOGICAL

375 mg/m2 IV Day 1 of each cycle

sargramostim

Intervention Type BIOLOGICAL

GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

cyclophosphamide

Intervention Type DRUG

750 mg/m2 IV Day 1 of each cycle

pegylated liposomal doxorubicin hydrochloride

Intervention Type DRUG

40 mg/m2 IV Day 1 of each cycle

prednisone

Intervention Type DRUG

100 mg PO Days 1-5 of each cycle

vincristine sulfate

Intervention Type DRUG

1.4 mg/m2 IV Day 1 (2.0 mg maximum) of each cycle

immunohistochemistry staining method

Intervention Type OTHER

tissue specimen collected at baseline

laboratory biomarker analysis

Intervention Type OTHER

tissue specimen collected at baseline

Interventions

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filgrastim

Supportive therapy: GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

Intervention Type BIOLOGICAL

pegfilgrastim

GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

Intervention Type BIOLOGICAL

rituximab

375 mg/m2 IV Day 1 of each cycle

Intervention Type BIOLOGICAL

sargramostim

GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

Intervention Type BIOLOGICAL

cyclophosphamide

750 mg/m2 IV Day 1 of each cycle

Intervention Type DRUG

pegylated liposomal doxorubicin hydrochloride

40 mg/m2 IV Day 1 of each cycle

Intervention Type DRUG

prednisone

100 mg PO Days 1-5 of each cycle

Intervention Type DRUG

vincristine sulfate

1.4 mg/m2 IV Day 1 (2.0 mg maximum) of each cycle

Intervention Type DRUG

immunohistochemistry staining method

tissue specimen collected at baseline

Intervention Type OTHER

laboratory biomarker analysis

tissue specimen collected at baseline

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

AIDS Malignancy Consortium

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alexandra M. Levine, MD

Role: STUDY_CHAIR

City of Hope Comprehensive Cancer Center

Locations

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Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

UCLA Clinical AIDS Research and Education (CARE) Center

Los Angeles, California, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Site Status

Ochsner Cancer Institute at Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Boston University Cancer Research Center

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Joan Karnell Cancer Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone in AIDS-related lymphoma: AIDS Malignancy Consortium Study 047. J Clin Oncol. 2013 Jan 1;31(1):58-64. doi: 10.1200/JCO.2012.42.4648. Epub 2012 Nov 19.

Reference Type RESULT
PMID: 23169503 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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U01CA070019

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000507634

Identifier Type: OTHER

Identifier Source: secondary_id

AMC-047

Identifier Type: -

Identifier Source: org_study_id

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