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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
filgrastim
pegfilgrastim
rituximab
sargramostim
cyclophosphamide
pegylated liposomal doxorubicin hydrochloride
prednisone
vincristine sulfate
immunohistochemistry staining method
laboratory biomarker analysis
Sponsored by
AIDS Malignancy Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, AIDS-related diffuse large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage I adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, AIDS-related immunoblastic large cell lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, AIDS-related peripheral/systemic lymphoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rebecca and John Moores UCSD Cancer Center
  • USC/Norris Comprehensive Cancer Center and Hospital
  • UCLA Clinical AIDS Research and Education (CARE) Center
  • University of Miami Sylvester Comprehensive Cancer Center - Miami
  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
  • Ochsner Cancer Institute at Ochsner Clinic Foundation
  • Boston University Cancer Research Center
  • Beth Israel Deaconess Medical Center
  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Albert Einstein Cancer Center at Albert Einstein College of Medicine
  • Memorial Sloan-Kettering Cancer Center
  • Case Comprehensive Cancer Center
  • Joan Karnell Cancer Center at Pennsylvania Hospital
  • Virginia Mason Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DR-COP

Arm Description

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

Outcomes

Primary Outcome Measures

Complete Response Rate (Complete Response and Complete Response Unconfirmed) Defined as Disappearance of All Evidence of Disease Based on Radiographic Findings on CT or MRI .
Duration of Response
Median Survival Time
Rate of Bacterial, Fungal, and Opportunistic Infections

Secondary Outcome Measures

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

Full Information

First Posted
October 18, 2006
Last Updated
May 3, 2018
Sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI), The Emmes Company, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00389818
Brief Title
Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed AIDS-Related B-Cell Non-Hodgkin's Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI), The Emmes Company, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, AIDS-related diffuse large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage I adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, AIDS-related immunoblastic large cell lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, AIDS-related peripheral/systemic lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DR-COP
Arm Type
Experimental
Arm Description
Single arm interventional study: all subjects receive DR-COP regimen.
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Description
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
Intervention Name(s)
pegfilgrastim
Intervention Description
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
Intervention Name(s)
rituximab
Intervention Description
375 mg/m2 IV Day 1 of each cycle
Intervention Type
Biological
Intervention Name(s)
sargramostim
Intervention Description
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
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
750 mg/m2 IV Day 1 of each cycle
Intervention Type
Drug
Intervention Name(s)
pegylated liposomal doxorubicin hydrochloride
Intervention Description
40 mg/m2 IV Day 1 of each cycle
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
100 mg PO Days 1-5 of each cycle
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Intervention Description
1.4 mg/m2 IV Day 1 (2.0 mg maximum) of each cycle
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Intervention Description
tissue specimen collected at baseline
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
tissue specimen collected at baseline
Primary Outcome Measure Information:
Title
Complete Response Rate (Complete Response and Complete Response Unconfirmed) Defined as Disappearance of All Evidence of Disease Based on Radiographic Findings on CT or MRI .
Time Frame
After cycles 2, 4, 6, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Title
Duration of Response
Time Frame
After cycles 2, 4, 6, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Title
Median Survival Time
Time Frame
After cycles 2, 4, 6, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Title
Rate of Bacterial, Fungal, and Opportunistic Infections
Time Frame
After every cycle of treatment, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Secondary Outcome Measure Information:
Title
Relationship Between MDR-1 Expression and Response to Treatment
Time Frame
Baseline
Title
Relationship Between Response and Survival and BCL-2 Expression in Tumor Tissue
Time Frame
Baseline, after cycles 4 and 6, 1 month after treatment discontinuation
Title
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
Time Frame
After every cycle of treatment, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Title
Mortality and Cause of Death
Time Frame
At any time through the third year after treatment discontinuation
Title
Event-free Survival at 1 Year
Time Frame
1 year post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandra M. Levine, MD
Organizational Affiliation
City of Hope Comprehensive Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Rebecca and John Moores UCSD Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
USC/Norris Comprehensive Cancer Center and Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089-9181
Country
United States
Facility Name
UCLA Clinical AIDS Research and Education (CARE) Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1793
Country
United States
Facility Name
University of Miami Sylvester Comprehensive Cancer Center - Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-3013
Country
United States
Facility Name
Ochsner Cancer Institute at Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Boston University Cancer Research Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Albert Einstein Cancer Center at Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States
Facility Name
Joan Karnell Cancer Center at Pennsylvania Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19106
Country
United States
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23169503
Citation
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.
Results Reference
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Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed AIDS-Related B-Cell Non-Hodgkin's Lymphoma

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