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

1 lutego 2018 zaktualizowane przez: 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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

60

Faza

  • Faza 2
  • Faza 1

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nielosowe
  • Model interwencyjny: Zadanie sekwencyjne
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: 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.
Lek: rituximab
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Lek: 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.
Lek: temozolomide 100 mg/m^2
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Promieniowanie: 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.
Inne nazwy:
  • radioterapia
Lek: 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.
Eksperymentalny: 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.
Lek: rituximab
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Lek: 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.
Promieniowanie: 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.
Inne nazwy:
  • radioterapia
Lek: 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.
Lek: temozolomide 150 mg/m^2
Temozolomide 150 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Eksperymentalny: 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.
Lek: rituximab
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Lek: 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.
Promieniowanie: 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.
Inne nazwy:
  • radioterapia
Lek: 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.
Lek: temozolomide 200 mg/m^2
Temozolomide 200 mg/m^2 per day by mouth for five days on weeks 4 and 8.
Eksperymentalny: 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.
Lek: rituximab
375 mg/m2, intravenously three days prior to the first cycle of methotrexate
Lek: 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.
Lek: temozolomide 100 mg/m^2
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
Promieniowanie: 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.
Inne nazwy:
  • radioterapia
Lek: 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.

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Number of Phase I Participants Experiencing Toxicity
Ramy czasowe: 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)
Ramy czasowe: 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.

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)
Ramy czasowe: 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)
Ramy czasowe: 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.

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Radiation Therapy Oncology Group

Współpracownicy

National Cancer Institute (NCI)
NRG Oncology

Śledczy

  • Krzesło do nauki: Jon Glass, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 lipca 2003

Zakończenie podstawowe (Rzeczywisty)

1 grudnia 2016

Ukończenie studiów (Rzeczywisty)

1 grudnia 2016

Daty rejestracji na studia

Pierwszy przesłany

10 września 2003

Pierwszy przesłany, który spełnia kryteria kontroli jakości

10 września 2003

Pierwszy wysłany (Oszacować)

11 września 2003

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

7 lutego 2018

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

1 lutego 2018

Ostatnia weryfikacja

1 lutego 2018

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • RTOG-0227
  • CDR0000301563

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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