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

2018. május 3. frissítette: 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.

A tanulmány áttekintése

Részletes leírás

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.

Tanulmány típusa

Beavatkozó

Beiratkozás (Tényleges)

43

Fázis

  • 2. fázis

Kapcsolatok és helyek

Ez a rész a vizsgálatot végzők elérhetőségeit, valamint a vizsgálat lefolytatásának helyére vonatkozó információkat tartalmazza.

Tanulmányi helyek

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

Részvételi kritériumok

A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.

Jogosultsági kritériumok

Tanulmányozható életkorok

18 év (Felnőtt, Idősebb felnőtt)

Egészséges önkénteseket fogad

Nem

Tanulmányozható nemek

Összes

Leírás

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

Tanulási terv

Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.

Hogyan készül a tanulmány?

Tervezési részletek

  • Elsődleges cél: Kezelés
  • Kiosztás: N/A
  • Beavatkozó modell: Egyetlen csoportos hozzárendelés
  • Maszkolás: Nincs (Open Label)

Fegyverek és beavatkozások

Résztvevő csoport / kar
Beavatkozás / kezelés
Kísérleti: 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

Mit mér a tanulmány?

Elsődleges eredményintézkedések

Eredménymérő
Időkeret
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 .
Időkeret: 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
Időkeret: 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
Időkeret: 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
Időkeret: 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

Másodlagos eredményintézkedések

Eredménymérő
Időkeret
Relationship Between MDR-1 Expression and Response to Treatment
Időkeret: Baseline
Baseline
Relationship Between Response and Survival and BCL-2 Expression in Tumor Tissue
Időkeret: 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
Időkeret: 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
Időkeret: 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
Időkeret: 1 year post-treatment
1 year post-treatment

Együttműködők és nyomozók

Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.

Nyomozók

  • Tanulmányi szék: Alexandra M. Levine, MD, City of Hope Comprehensive Cancer Center

Publikációk és hasznos linkek

A vizsgálattal kapcsolatos információk beviteléért felelős személy önkéntesen bocsátja rendelkezésre ezeket a kiadványokat. Ezek bármiről szólhatnak, ami a tanulmányhoz kapcsolódik.

Tanulmányi rekorddátumok

Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.

Tanulmány főbb dátumok

Tanulmány kezdete

2007. január 1.

Elsődleges befejezés (Tényleges)

2011. szeptember 1.

A tanulmány befejezése (Tényleges)

2011. szeptember 1.

Tanulmányi regisztráció dátumai

Először benyújtva

2006. október 18.

Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak

2006. október 18.

Első közzététel (Becslés)

2006. október 19.

Tanulmányi rekordok frissítései

Utolsó frissítés közzétéve (Tényleges)

2018. június 6.

Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak

2018. május 3.

Utolsó ellenőrzés

2018. május 1.

Több információ

A tanulmányhoz kapcsolódó kifejezések

Egyéb vizsgálati azonosító számok

  • AMC-047
  • U01CA070019 (Az Egyesült Államok NIH támogatása/szerződése)
  • CDR0000507634 (Egyéb azonosító: NCI)

Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .

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