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

1 juli 2016 bijgewerkt door: 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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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

Ingrijpend

Inschrijving (Werkelijk)

47

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

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

  • Kind
  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

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: 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)
Biologisch: 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)
Andere namen:
  • G-CSF
Biologisch: 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
Geneesmiddel: cytarabine
2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6
Geneesmiddel: etoposide
5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6
Geneesmiddel: 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.
Geneesmiddel: 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.
Geneesmiddel: temozolomide
150 mg/sq m PO Days 7-11 Cycles 1-5.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Complete Response Rate After Remission Induction
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
4 Year Progression Free Rate
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

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

Sponsor

Alliance for Clinical Trials in Oncology

Medewerkers

National Cancer Institute (NCI)

Onderzoekers

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

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.

Algemene publicaties

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 oktober 2004

Primaire voltooiing (Werkelijk)

1 januari 2010

Studie voltooiing (Werkelijk)

1 september 2014

Studieregistratiedata

Eerst ingediend

8 december 2004

Eerst ingediend dat voldeed aan de QC-criteria

8 december 2004

Eerst geplaatst (Schatting)

9 december 2004

Updates van studierecords

Laatste update geplaatst (Schatting)

6 juli 2016

Laatste update ingediend die voldeed aan QC-criteria

1 juli 2016

Laatst geverifieerd

1 juli 2016

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • CALGB-50202
  • U10CA031946 (Subsidie/contract van de Amerikaanse NIH)
  • CDR0000398106 (Register-ID: NCI Physician Data Query)

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 .

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