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Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed AIDS-Related B-Cell Non-Hodgkin's Lymphoma
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
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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
- Biologisch: filgrastim
- Biologisch: pegfilgrastim
- Biologisch: rituximab
- Biologisch: sargramostim
- Geneesmiddel: cyclophosphamide
- Geneesmiddel: pegylated liposomal doxorubicin hydrochloride
- Geneesmiddel: prednisone
- Geneesmiddel: vincristine sulfate
- Ander: immunohistochemistry staining method
- Ander: laboratory biomarker analysis
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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California
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La Jolla, California, Verenigde Staten, 92093-0658
- Rebecca and John Moores UCSD Cancer Center
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Los Angeles, California, Verenigde Staten, 90089-9181
- USC/Norris Comprehensive Cancer Center and Hospital
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Los Angeles, California, Verenigde Staten, 90095-1793
- UCLA Clinical AIDS Research and Education (CARE) Center
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Florida
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Miami, Florida, Verenigde Staten, 33136
- University of Miami Sylvester Comprehensive Cancer Center - Miami
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Illinois
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Chicago, Illinois, Verenigde Staten, 60611-3013
- Robert H. Lurie Comprehensive Cancer Center at Northwestern University
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Louisiana
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New Orleans, Louisiana, Verenigde Staten, 70121
- Ochsner Cancer Institute at Ochsner Clinic Foundation
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Verenigde Staten, 02118
- Boston University Cancer Research Center
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Missouri
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Saint Louis, Missouri, Verenigde Staten, 63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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New York
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Bronx, New York, Verenigde Staten, 10461
- Albert Einstein Cancer Center at Albert Einstein College of Medicine
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New York, New York, Verenigde Staten, 10065
- Memorial Sloan-Kettering Cancer Center
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Ohio
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Cleveland, Ohio, Verenigde Staten, 44106-5065
- Case Comprehensive Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, Verenigde Staten, 19106
- Joan Karnell Cancer Center at Pennsylvania Hospital
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Washington
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Seattle, Washington, Verenigde Staten, 98101
- Virginia Mason Medical Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: DR-COP
Single arm interventional study: all subjects receive DR-COP regimen.
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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.
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.
375 mg/m2 IV Day 1 of each cycle
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.
750 mg/m2 IV Day 1 of each cycle
40 mg/m2 IV Day 1 of each cycle
100 mg PO Days 1-5 of each cycle
1.4 mg/m2 IV Day 1 (2.0 mg maximum) of each cycle
tissue specimen collected at baseline
tissue specimen collected at baseline
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
---|---|
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 .
Tijdsspanne: 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
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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
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Duration of Response
Tijdsspanne: 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
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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
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Median Survival Time
Tijdsspanne: 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
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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
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Rate of Bacterial, Fungal, and Opportunistic Infections
Tijdsspanne: 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
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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
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Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
---|---|
Relationship Between MDR-1 Expression and Response to Treatment
Tijdsspanne: Baseline
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Baseline
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Relationship Between Response and Survival and BCL-2 Expression in Tumor Tissue
Tijdsspanne: Baseline, after cycles 4 and 6, 1 month after treatment discontinuation
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Baseline, after cycles 4 and 6, 1 month after treatment discontinuation
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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
Tijdsspanne: 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
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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
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Mortality and Cause of Death
Tijdsspanne: At any time through the third year after treatment discontinuation
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At any time through the third year after treatment discontinuation
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Event-free Survival at 1 Year
Tijdsspanne: 1 year post-treatment
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1 year post-treatment
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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie stoel: Alexandra M. Levine, MD, City of Hope Comprehensive Cancer Center
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
- stadium III volwassen diffuus grootcellig lymfoom
- stadium III volwassen immunoblastisch grootcellig lymfoom
- stadium IV graad 3 folliculair lymfoom
- stadium IV volwassen diffuus grootcellig lymfoom
- stadium IV volwassen immunoblastisch grootcellig lymfoom
- AIDS-gerelateerd perifeer/systemisch lymfoom
- AIDS-gerelateerd diffuus grootcellig lymfoom
- AIDS-gerelateerd immunoblastisch grootcellig lymfoom
- stadium III graad 3 folliculair lymfoom
- niet-aaneengesloten stadium II volwassen diffuus grootcellig lymfoom
- niet-aangrenzend stadium II graad 3 folliculair lymfoom
- niet-aaneengesloten stadium II volwassen immunoblastisch grootcellig lymfoom
- aaneengesloten stadium II volwassen immunoblastisch grootcellig lymfoom
- stadium I volwassen immunoblastisch grootcellig lymfoom
- aaneengesloten stadium II graad 3 folliculair lymfoom
- stadium I graad 3 folliculair lymfoom
- aaneengesloten stadium II volwassen diffuus grootcellig lymfoom
- stadium I volwassen diffuus grootcellig lymfoom
Aanvullende relevante MeSH-voorwaarden
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Neoplasmata
- Lymfoproliferatieve aandoeningen
- Lymfatische ziekten
- Immunoproliferatieve aandoeningen
- Lymfoom
- Lymfoom, B-cel
- Lymfoom, non-Hodgkin
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Ontstekingsremmende middelen
- Antireumatische middelen
- Antineoplastische middelen
- Immunosuppressieve middelen
- Immunologische factoren
- Tubuline-modulatoren
- Antimitotische middelen
- Mitose modulatoren
- Glucocorticoïden
- Hormonen
- Hormonen, hormoonvervangers en hormoonantagonisten
- Antineoplastische middelen, hormonaal
- Antineoplastische middelen, alkylering
- Alkyleringsmiddelen
- Myeloablatieve agonisten
- Antineoplastische middelen, fytogeen
- Topoisomerase II-remmers
- Topoisomeraseremmers
- Antineoplastische middelen, immunologisch
- Antibiotica, antineoplastiek
- Cyclofosfamide
- Rituximab
- Prednison
- Doxorubicine
- Liposomale doxorubicine
- Vincristine
- Sargramostim
Andere studie-ID-nummers
- AMC-047
- U01CA070019 (Subsidie/contract van de Amerikaanse NIH)
- CDR0000507634 (Andere identificatie: NCI)
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