Deze pagina is automatisch vertaald en de nauwkeurigheid van de vertaling kan niet worden gegarandeerd. Raadpleeg de Engelse versie voor een brontekst.

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

3 mei 2018 bijgewerkt door: AIDS Malignancy Consortium

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

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

Ingrijpend

Inschrijving (Werkelijk)

43

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

    • California
      • La Jolla, California, Verenigde Staten, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center
      • Los Angeles, California, Verenigde Staten, 90089-9181
        • USC/Norris Comprehensive Cancer Center and Hospital
      • Los Angeles, California, Verenigde Staten, 90095-1793
        • UCLA Clinical AIDS Research and Education (CARE) Center
    • Florida
      • Miami, Florida, Verenigde Staten, 33136
        • University of Miami Sylvester Comprehensive Cancer Center - Miami
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60611-3013
        • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Louisiana
      • New Orleans, Louisiana, Verenigde Staten, 70121
        • Ochsner Cancer Institute at Ochsner Clinic Foundation
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, Verenigde Staten, 02118
        • Boston University Cancer Research Center
    • Missouri
      • Saint Louis, Missouri, Verenigde Staten, 63110
        • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • New York
      • Bronx, New York, Verenigde Staten, 10461
        • Albert Einstein Cancer Center at Albert Einstein College of Medicine
      • New York, New York, Verenigde Staten, 10065
        • Memorial Sloan-Kettering Cancer Center
    • Ohio
      • Cleveland, Ohio, Verenigde Staten, 44106-5065
        • Case Comprehensive Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Verenigde Staten, 19106
        • Joan Karnell Cancer Center at Pennsylvania Hospital
    • Washington
      • Seattle, Washington, Verenigde Staten, 98101
        • Virginia Mason Medical Center

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 120 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

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

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

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

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
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
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
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
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
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
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
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

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Relationship Between MDR-1 Expression and Response to Treatment
Tijdsspanne: Baseline
Baseline
Relationship Between Response and Survival and BCL-2 Expression in Tumor Tissue
Tijdsspanne: Baseline, after cycles 4 and 6, 1 month after treatment discontinuation
Baseline, after cycles 4 and 6, 1 month after treatment discontinuation
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
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
Mortality and Cause of Death
Tijdsspanne: At any time through the third year after treatment discontinuation
At any time through the third year after treatment discontinuation
Event-free Survival at 1 Year
Tijdsspanne: 1 year post-treatment
1 year post-treatment

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Onderzoekers

  • Studie stoel: Alexandra M. Levine, MD, City of Hope Comprehensive Cancer Center

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 januari 2007

Primaire voltooiing (Werkelijk)

1 september 2011

Studie voltooiing (Werkelijk)

1 september 2011

Studieregistratiedata

Eerst ingediend

18 oktober 2006

Eerst ingediend dat voldeed aan de QC-criteria

18 oktober 2006

Eerst geplaatst (Schatting)

19 oktober 2006

Updates van studierecords

Laatste update geplaatst (Werkelijk)

6 juni 2018

Laatste update ingediend die voldeed aan QC-criteria

3 mei 2018

Laatst geverifieerd

1 mei 2018

Meer informatie

Termen gerelateerd aan deze studie

Andere studie-ID-nummers

  • AMC-047
  • U01CA070019 (Subsidie/contract van de Amerikaanse NIH)
  • CDR0000507634 (Andere identificatie: NCI)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Klinische onderzoeken op filgrastim

3
Abonneren