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Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma

1. Februar 2018 aktualisiert von: Radiation Therapy Oncology Group

Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma

RATIONALE: Drugs used in chemotherapy such as methotrexate and temozolomide use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining methotrexate, temozolomide, and rituximab with radiation therapy may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of temozolomide when given together with methotrexate and rituximab followed by radiation therapy and to see how well they work in treating patients with primary central nervous system lymphoma.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

OBJECTIVES:

  • To assess the maximum tolerated dose (MTD) of temozolomide (TMZ) in combination with methotrexate (MTX) and rituximab (RTX) when administered prior to twice daily fractionated whole brain radiation therapy (WBRT) in patients with primary central nervous system lymphoma.
  • To compare the two-year survival rate in patients receiving pre-irradiation chemotherapy, twice daily fractionated whole brain radiation therapy and post-irradiation temozolomide to the reported two-year survival rate of Radiation Therapy Oncology Group (RTOG) trial 93-10. RTOG 9310 does not fall within ClinicalTrials.gov registration/reporting requirements.)
  • To compare the pre-irradiation chemotherapy tumor response rates to the reported rate from RTOG 93-10.
  • To report progression-free survival.
  • To assess acute and long-term neurologic toxicity, and to collect quality of life data for this patient group.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

60

Phase

  • Phase 2
  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Vereinigte Staaten
    • Florida
      • Jacksonville, Florida, Vereinigte Staaten, 32207
        • Baptist Cancer Institute - Jacksonville
      • Jacksonville, Florida, Vereinigte Staaten, 32207
        • Integrated Community Oncology Network at Southside Cancer Center
      • Jacksonville, Florida, Vereinigte Staaten, 32258
        • Baptist Medical Center South
      • Jacksonville Beach, Florida, Vereinigte Staaten, 32250
        • Integrated Community Oncology Network
      • Orange Park, Florida, Vereinigte Staaten, 32073
        • Integrated Community Oncology Network - Orange Park
      • Palatka, Florida, Vereinigte Staaten, 32177
        • Florida Cancer Center - Palatka
      • Saint Augustine, Florida, Vereinigte Staaten, 32086
        • Flagler Cancer Center
    • Michigan
      • Kalamazoo, Michigan, Vereinigte Staaten, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, Vereinigte Staaten, 49001
        • Borgess Medical Center
      • Kalamazoo, Michigan, Vereinigte Staaten, 49007-3731
        • West Michigan Cancer Center
    • Missouri
      • Kansas City, Missouri, Vereinigte Staaten, 64131
        • CCOP - Kansas City
      • Saint Louis, Missouri, Vereinigte Staaten, 63110
        • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • Nevada
      • Las Vegas, Nevada, Vereinigte Staaten, 89106
        • CCOP - Nevada Cancer Research Foundation
    • New Jersey
      • Edison, New Jersey, Vereinigte Staaten, 08818
        • John F. Kennedy Medical Center
    • Ohio
      • Cleveland, Ohio, Vereinigte Staaten, 44195
        • Cleveland Clinic Taussig Cancer Center
    • Oregon
      • Milwaukie, Oregon, Vereinigte Staaten, 97222
        • Providence Milwaukie Hospital
      • Portland, Oregon, Vereinigte Staaten, 97213-2967
        • Providence Cancer Center at Providence Portland Medical Center
      • Portland, Oregon, Vereinigte Staaten, 97225
        • CCOP - Columbia River Oncology Program
      • Portland, Oregon, Vereinigte Staaten, 97225
        • Providence St. Vincent Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Vereinigte Staaten, 19107-5541
        • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • South Carolina
      • Charleston, South Carolina, Vereinigte Staaten, 29425
        • Hollings Cancer Center at Medical University of South Carolina
    • Utah
      • Murray, Utah, Vereinigte Staaten, 84157
        • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
      • Provo, Utah, Vereinigte Staaten, 84604
        • Utah Valley Regional Medical Center - Provo
    • Washington
      • Vancouver, Washington, Vereinigte Staaten, 98668
        • Southwest Washington Medical Center Cancer Center
    • Wisconsin
      • Menomonee Falls, Wisconsin, Vereinigte Staaten, 53051
        • Community Memorial Hospital Cancer Care Center
      • Milwaukee, Wisconsin, Vereinigte Staaten, 53226
        • Medical College of Wisconsin Cancer Center

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion criteria:

  1. Primary central nervous system (CNS) lymphoma [B-cell, Cluster of Differentiation 20 (CD20) antigen positive] based on positive biopsy or cerebrospinal fluid (CSF) or vitreous cytology (in association with measurable intraparenchymal tumor). Cytology must demonstrate lymphoma or have an immunohistochemical diagnosis of malignant lymphocytes with a monoclonal lymphocytic population.
  2. Life expectancy ≥ 8 weeks;
  3. Zubrod performance status of 0-2;
  4. Absolute granulocyte count ≥1500/mm3; platelet count ≥ 100,000/mm3; creatinine clearance ≥ 50, calculated with the Cockcroft-Gault Equation: Cr Clearance = (140-age) x wt (kg)/(Cr[mg/dl]x 72); Bilirubin, serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (AST) ≤ 2 x institutional upper limits of normal;
  5. Patients must sign a study-specific informed consent prior to study entry.
  6. Age ≥ 18

Exclusion criteria:

  1. Evidence of systemic lymphoma;
  2. Prior malignancy (excluding in situ carcinoma of the cervix or non-melanomatous skin cancer)unless disease free for at least five years;
  3. Prior radiotherapy to the brain or head/neck;
  4. Prior chemotherapy;
  5. History of idiopathic sensitivity to any of the drugs to be used;
  6. Active infectious process;
  7. Seropositive for HIV, AIDS, or post-organ transplant;
  8. Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus.
  9. Active hepatitis B.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Nicht randomisiert
  • Interventionsmodell: Sequenzielle Zuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Phase I: Temozolomide 100 mg
Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
Arzneimittel: rituximab
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Arzneimittel: methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Arzneimittel: temozolomide 100 mg/m^2
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Strahlung: radiation therapy
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
Andere Namen:
  • Strahlentherapie
Arzneimittel: post-radiation therapy temozolomide
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
Experimental: Phase I: Temozolomide 150 mg
Rituximab, methotrexate, temozolomide 150 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
Arzneimittel: rituximab
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Arzneimittel: methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Strahlung: radiation therapy
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
Andere Namen:
  • Strahlentherapie
Arzneimittel: post-radiation therapy temozolomide
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
Arzneimittel: temozolomide 150 mg/m^2
Temozolomide 150 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Experimental: Phase I: Temozolomide 200 mg
Rituximab, methotrexate, temozolomide 200 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
Arzneimittel: rituximab
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Arzneimittel: methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Strahlung: radiation therapy
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
Andere Namen:
  • Strahlentherapie
Arzneimittel: post-radiation therapy temozolomide
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.
Arzneimittel: temozolomide 200 mg/m^2
Temozolomide 200 mg/m^2 per day by mouth for five days on weeks 4 and 8.
Experimental: Phase II: Temozolomide 100 mg
Rituximab, methotrexate, temozolomide 100 mg/m^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m^2.
Arzneimittel: rituximab
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Arzneimittel: methotrexate
Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar.
Arzneimittel: temozolomide 100 mg/m^2
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Strahlung: radiation therapy
Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy.
Andere Namen:
  • Strahlentherapie
Arzneimittel: post-radiation therapy temozolomide
Temozolomide (TMZ) 200 mg/m^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of Phase I Participants Experiencing Toxicity
Zeitfenster: From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
A dose limiting toxicity (DLT) is defined as any grade 3 or 4 non-hematological toxicity (other than grade 3 nausea/vomiting) or any hematological toxicity resulting in the discontinuation of temozolomide. Toxicity evaluation for this dose escalation includes all toxicities occurring prior to the start of radiation therapy. If the patient did not receive radiation therapy, then toxicity evaluation included all toxicities occurring through week 15. Any grade 5 toxicity would result in immediate suspension of accrual.
From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)
Zeitfenster: Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (Please note that this outcome measure is considered the primary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )
Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)
Zeitfenster: From start of treatment to 10 weeks if RT received, to 15 weeks if not.
Tumor response was centrally reviewed. Complete response: Disappearance of all enhancing tumor, the patient must be off steroid therapy and neurologically stable or improved; partial response: ≥ 50% decrease in enhancing tumor; progressive disease: ≥ 25% increase in a lesion, progressive or newly emergent meningeal or ocular disease. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )
From start of treatment to 10 weeks if RT received, to 15 weeks if not.
Phase II: Progression-free Survival (Including Phase I Patients at Same Dose)
Zeitfenster: Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
Progression is defined as greater than 25% increase in enhancing tumor or the appearance of new lesions in the brain, eye, or the appearance of a new positive cerebrospinal fluid (CSF) cytology. The patient may be neurologically stable or worse and on stable or increasing doses of corticosteroid. Progression-free survival time is defined as time from registration to the date of progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )
Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Radiation Therapy Oncology Group

Mitarbeiter

National Cancer Institute (NCI)
NRG Oncology

Ermittler

  • Studienstuhl: Jon Glass, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. Juli 2003

Primärer Abschluss (Tatsächlich)

1. Dezember 2016

Studienabschluss (Tatsächlich)

1. Dezember 2016

Studienanmeldedaten

Zuerst eingereicht

10. September 2003

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

10. September 2003

Zuerst gepostet (Schätzen)

11. September 2003

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

7. Februar 2018

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

1. Februar 2018

Zuletzt verifiziert

1. Februar 2018

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • RTOG-0227
  • CDR0000301563

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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