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Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Primary CNS Lymphoma

1. juli 2016 oppdatert av: Alliance for Clinical Trials in Oncology

Intensive Chemotherapy And Immunotherapy In Patients With Newly Diagnosed Primary CNS 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 block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving rituximab with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well rituximab given with combination chemotherapy works in treating patients with newly diagnosed primary CNS lymphoma.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

OBJECTIVES:

Primary

  • Determine the complete response rate after remission induction therapy with the combination of high-dose methotrexate (HDMTX), temozolomide, and rituximab at 4 months.

Secondary

  • Determine the safety and feasibility of consolidation therapy comprising cytarabine and etoposide administered after induction therapy in these patients.
  • Determine the percentage of patients who achieve durable (complete and partial) remission when treated with this regimen.
  • Determine relapse-free survival after complete response in patients treated with this regimen.
  • Correlate molecular markers with outcome in patients treated with this regimen.
  • Determine the effects of this regimen on neurological function in these patients.

OUTLINE: This is a multicenter study.

  • Induction Chemotherapy: All induction therapy courses repeat every 28 days.

    • Courses 1-3: Patients receive high-dose methotrexate IV over 4 hours on days 1 and 15, leucovorin calcium IV or orally every 6 hours beginning on days 2 and 16 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11. Patients also receive rituximab* IV on days 3, 10, 17, and 24 of course 1 and days 3 and 10 of course 2 (total of 6 doses).

NOTE: *Patients diagnosed with T-cell primary CNS lymphoma do not receive rituximab.

  • Course 4: Patients receive oral temozolomide on days 7-11, high-dose methotrexate IV over 4 hours on day 15, and leucovorin calcium IV or orally every 6 hours beginning on day 16 and continuing until blood levels of methotrexate are in a safe range. Patients achieving a complete response or a complete response unconfirmed proceed to consolidation therapy.

    • Consolidation therapy I (course 5): Beginning 4 weeks after the start of course 4, patients receive high-dose methotrexate IV over 4 hours on day 1, leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11.
    • Consolidation therapy II (course 6): Beginning 3-5 weeks after the start of course 5, patients receive cytarabine IV over 2 hours twice daily and etoposide IV over 12 hours twice daily on days 1-4 and filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning on day 14 and continuing until blood counts recover.

Treatment continues in the absence of disease progression.

After completion of study treatment, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 27-45 patients will be accrued for this study within 2-3 years.

Studietype

Intervensjonell

Registrering (Faktiske)

47

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • California
      • San Francisco, California, Forente stater, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Delaware
      • Lewes, Delaware, Forente stater, 19958
        • Tunnell Cancer Center at Beebe Medical Center
      • Newark, Delaware, Forente stater, 19713
        • CCOP - Christiana Care Health Services
    • Illinois
      • Chicago, Illinois, Forente stater, 60637-1470
        • University of Chicago Cancer Research Center
    • Indiana
      • Fort Wayne, Indiana, Forente stater, 46845
        • Fort Wayne Medical Oncology and Hematology
    • Iowa
      • Bettendorf, Iowa, Forente stater, 52722
        • Hematology Oncology Associates of the Quad Cities
    • Kansas
      • Overland Park, Kansas, Forente stater, 66209
        • Menorah Medical Center
      • Overland Park, Kansas, Forente stater, 66213
        • Saint Luke's Hospital - South
      • Shawnee Mission, Kansas, Forente stater, 66204
        • Shawnee Mission Medical Center
    • Maryland
      • Elkton MD, Maryland, Forente stater, 21921
        • Union Hospital Cancer Program at Union Hospital
    • Minnesota
      • Minneapolis, Minnesota, Forente stater, 55455
        • Masonic Cancer Center at University of Minnesota
    • Missouri
      • Kansas City, Missouri, Forente stater, 64131
        • CCOP - Kansas City
      • Kansas City, Missouri, Forente stater, 64116
        • North Kansas City Hospital
      • Kansas City, Missouri, Forente stater, 64132
        • Research Medical Center
      • Kansas City, Missouri, Forente stater, 64108
        • Truman Medical Center - Hospital Hill
      • Kansas City, Missouri, Forente stater, 64111
        • Saint Luke's Cancer Institute at Saint Luke's Hospital
      • Kansas City, Missouri, Forente stater, 64114
        • St. Joseph Medical Center
      • Kansas City, Missouri, Forente stater, 64116
        • Parvin Radiation Oncology
      • Lee's Summit, Missouri, Forente stater, 64086
        • Saint Luke's East - Lee's Summit
      • Liberty, Missouri, Forente stater, 64068
        • Liberty Hospital
      • Saint Joseph, Missouri, Forente stater, 64506
        • Heartland Regional Medical Center
    • New Jersey
      • Voorhees, New Jersey, Forente stater, 08043
        • Cancer Institute of New Jersey at Cooper - Voorhees
    • New York
      • Stony Brook, New York, Forente stater, 11794-9446
        • Stony Brook University Cancer Center
      • Syracuse, New York, Forente stater, 13210
        • SUNY Upstate Medical University Hospital
    • Ohio
      • Columbus, Ohio, Forente stater, 43210-1240
        • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
    • Rhode Island
      • Providence, Rhode Island, Forente stater, 02906
        • Miriam Hospital
      • Providence, Rhode Island, Forente stater, 02903
        • Rhode Island Hospital Comprehensive Cancer Center
    • Vermont
      • Berlin, Vermont, Forente stater, 05602
        • Mountainview Medical
      • Burlington, Vermont, Forente stater, 05401
        • Fletcher Allen Health Care - University Health Center Campus
    • Virginia
      • Danville, Virginia, Forente stater, 24541
        • Danville Regional Medical Center

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Barn
  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

DISEASE CHARACTERISTICS:

  • Histologically confirmed newly diagnosed primary CNS lymphoma confirmed by 1 of the following methods:

    • Brain biopsy or resection

    • Cerebrospinal fluid (CSF) cytology

      • Positive CSF cytology with or without measurable intracranial disease

  • No evidence of systemic non-Hodgkin's lymphoma

    • CT scan or MRI of the chest, abdomen, and pelvis AND bilateral bone marrow biopsy or unilateral biopsy with a 2cm core biopsy specimen that is negative for extracerebral source of lymphoma
  • Measurable contrast-enhancing disease by MRI of the brain and spine (plus gadolinium) unless CSF cytology positive
  • No evidence of pleural effusions or ascites

PATIENT CHARACTERISTICS:

Age

  • Any age

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

  • ALT and AST ≤ 2 times upper limit of normal
  • Bilirubin ≤ 2 mg/dL

Renal

  • Creatinine clearance ≥ 50 mL/min

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 6 months after study participation
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Not specified

Endocrine therapy

  • Concurrent steroids for the management of symptoms related to lymphoma allowed

Radiotherapy

  • No concurrent palliative radiotherapy

Surgery

  • Not specified

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Intensive Combination Chemo & Immunotherapy

Induction Cycles 1-3: Methotrexate 8gm/m^2 days 1 & 15; Leucovorin 100 mg/m^2 days 2 & 16; Rituximab 375 mg/m^2 days 3, 10, 17 & 24 of cycle 1, days 3 & 10 of cycle 2; Temozolomide 150 mg/m^2/day PO days 7-11

Induction Cycle 4: Temozolomide 150 mg/m^2/day PO days 7-11; Methotrexate 8gm/m^2 day 15; Leucovorin 100 mg/m^2 day 16

Consolidation Cycle 5: Methotrexate 8gm/m^2 days 1; Leucovorin 100 mg/m^2 days 2; Temozolomide 150 mg/m^2/day PO days 7-11

Consolidation Cycle 6: Cytarabine 2 g/m^2 (x 8 doses) days 1-4; Etoposide 5 mg/kg (x 8 doses) days 1-4; G-CSF 5 mcg/kg/day or GM-CSF 250 mcg/m^2/day starting day 14 until ANC recovers (>= 500 for 2 consecutive days or >= 1500 for one day)
Biologisk: filgrastim
5 mcg/kg subQ injection daily Day 14 until ANC > or = 500 uL for 2 days or 1500 uL for 1 day (Cycle 6)
Andre navn:
  • G-CSF
Biologisk: rituximab
375 mg/sq m IV infusion (max rate of 400 mg/hr) on Days 3, 10, 17, & 24 of Cycle 1 nad Days 3 & 10 of Cycle 2
Legemiddel: cytarabine
2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6
Legemiddel: etoposide
5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6
Legemiddel: leucovorin calcium
100 mg/sq m IV infusion q 6 hrs starting 24 hrs after ea MTX dose until serum MTX < or = 0.05uM Cycles 1-5.
Legemiddel: methotrexate
8 g/sq m IV infusion over 4 hrs Days 1 & 15 Cycles 1, 2, & 3; Day 15 Cycle 4 and Day 1 Cycle 5.
Legemiddel: temozolomide
150 mg/sq m PO Days 7-11 Cycles 1-5.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Complete Response Rate After Remission Induction
Tidsramme: 4 months
Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Complete response requires disappearance of all evidence of disease.
4 months

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
4 Year Progression Free Rate
Tidsramme: 4 years

Percentage of patients who were progression free at 4 years. The 4-year progression free rate was estimated using the Kaplan Meier method.

Relapse was assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Progression required a 25% increase of previous area of gadolinium enhancement, appearance of new areas of T1 gadolinium enhancement or new appearance of malignant cells in the spinal fluid or new tumor appearance in other sites of the body
4 years
Change From Baseline in Mini-Mental Status Evaluation at 4 Months
Tidsramme: Baseline & month 4
Neurologic functioning will be assessed using the Mini-Mental Status Evaluation (MMSE), a standardized, bedside tool for evaluation of higher mental function. This assessment is based on a 30-point scale (0-30) with higher scores associated with better performance.
Baseline & month 4
4 Year Overall Survival Rate
Tidsramme: 4 years
Percentage of patients who were alive at 4 years. The 4-year survival rate was estimated using the Kaplan Meier method.
4 years

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Alliance for Clinical Trials in Oncology

Samarbeidspartnere

National Cancer Institute (NCI)

Etterforskere

  • Studiestol: James Rubenstein, MD, PhD, University of California, San Francisco

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. oktober 2004

Primær fullføring (Faktiske)

1. januar 2010

Studiet fullført (Faktiske)

1. september 2014

Datoer for studieregistrering

Først innsendt

8. desember 2004

Først innsendt som oppfylte QC-kriteriene

8. desember 2004

Først lagt ut (Anslag)

9. desember 2004

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

6. juli 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

1. juli 2016

Sist bekreftet

1. juli 2016

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • CALGB-50202
  • U10CA031946 (U.S. NIH-stipend/kontrakt)
  • CDR0000398106 (Registeridentifikator: NCI Physician Data Query)

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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