Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma
1 febbraio 2018 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
60
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Florida
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Jacksonville, Florida, Stati Uniti, 32207
- Baptist Cancer Institute - Jacksonville
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Jacksonville, Florida, Stati Uniti, 32207
- Integrated Community Oncology Network at Southside Cancer Center
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Jacksonville, Florida, Stati Uniti, 32258
- Baptist Medical Center South
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Jacksonville Beach, Florida, Stati Uniti, 32250
- Integrated Community Oncology Network
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Orange Park, Florida, Stati Uniti, 32073
- Integrated Community Oncology Network - Orange Park
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Palatka, Florida, Stati Uniti, 32177
- Florida Cancer Center - Palatka
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Saint Augustine, Florida, Stati Uniti, 32086
- Flagler Cancer Center
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Michigan
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Kalamazoo, Michigan, Stati Uniti, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Stati Uniti, 49001
- Borgess Medical Center
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Kalamazoo, Michigan, Stati Uniti, 49007-3731
- West Michigan Cancer Center
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Missouri
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Kansas City, Missouri, Stati Uniti, 64131
- CCOP - Kansas City
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Saint Louis, Missouri, Stati Uniti, 63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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Nevada
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Las Vegas, Nevada, Stati Uniti, 89106
- CCOP - Nevada Cancer Research Foundation
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New Jersey
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Edison, New Jersey, Stati Uniti, 08818
- John F. Kennedy Medical Center
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Ohio
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Cleveland, Ohio, Stati Uniti, 44195
- Cleveland Clinic Taussig Cancer Center
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Oregon
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Milwaukie, Oregon, Stati Uniti, 97222
- Providence Milwaukie Hospital
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Portland, Oregon, Stati Uniti, 97213-2967
- Providence Cancer Center at Providence Portland Medical Center
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Portland, Oregon, Stati Uniti, 97225
- CCOP - Columbia River Oncology Program
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Portland, Oregon, Stati Uniti, 97225
- Providence St. Vincent Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti, 19107-5541
- Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
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South Carolina
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Charleston, South Carolina, Stati Uniti, 29425
- Hollings Cancer Center at Medical University of South Carolina
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Utah
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Murray, Utah, Stati Uniti, 84157
- Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
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Provo, Utah, Stati Uniti, 84604
- Utah Valley Regional Medical Center - Provo
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Washington
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Vancouver, Washington, Stati Uniti, 98668
- Southwest Washington Medical Center Cancer Center
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Wisconsin
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Menomonee Falls, Wisconsin, Stati Uniti, 53051
- Community Memorial Hospital Cancer Care Center
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Milwaukee, Wisconsin, Stati Uniti, 53226
- Medical College of Wisconsin Cancer Center
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion criteria:
- 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.
- Life expectancy ≥ 8 weeks;
- Zubrod performance status of 0-2;
- 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;
- Patients must sign a study-specific informed consent prior to study entry.
- Age ≥ 18
Exclusion criteria:
- Evidence of systemic lymphoma;
- Prior malignancy (excluding in situ carcinoma of the cervix or non-melanomatous skin cancer)unless disease free for at least five years;
- Prior radiotherapy to the brain or head/neck;
- Prior chemotherapy;
- History of idiopathic sensitivity to any of the drugs to be used;
- Active infectious process;
- Seropositive for HIV, AIDS, or post-organ transplant;
- Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus.
- Active hepatitis B.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione sequenziale
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: 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.
|
375 mg/m2, intravenously three days prior to the first cycle of 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.
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
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.
Altri nomi:
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.
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|
Sperimentale: 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.
|
375 mg/m2, intravenously three days prior to the first cycle of 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.
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.
Altri nomi:
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.
Temozolomide 150 mg/m^2 by mouth per day for five days on weeks 4 and 8.
|
|
Sperimentale: 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.
|
375 mg/m2, intravenously three days prior to the first cycle of 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.
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.
Altri nomi:
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.
Temozolomide 200 mg/m^2 per day by mouth for five days on weeks 4 and 8.
|
|
Sperimentale: 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.
|
375 mg/m2, intravenously three days prior to the first cycle of 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.
Temozolomide 100 mg/m^2 by mouth per day for five days on weeks 4 and 8.
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.
Altri nomi:
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.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Number of Phase I Participants Experiencing Toxicity
Lasso di tempo: From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
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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.
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From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.
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Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)
Lasso di tempo: 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.
)
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Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose)
Lasso di tempo: 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.
)
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From start of treatment to 10 weeks if RT received, to 15 weeks if not.
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Phase II: Progression-free Survival (Including Phase I Patients at Same Dose)
Lasso di tempo: 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.
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Investigatori
- Cattedra di studio: Jon Glass, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 luglio 2003
Completamento primario (Effettivo)
1 dicembre 2016
Completamento dello studio (Effettivo)
1 dicembre 2016
Date di iscrizione allo studio
Primo inviato
10 settembre 2003
Primo inviato che soddisfa i criteri di controllo qualità
10 settembre 2003
Primo Inserito (Stima)
11 settembre 2003
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
7 febbraio 2018
Ultimo aggiornamento inviato che soddisfa i criteri QC
1 febbraio 2018
Ultimo verificato
1 febbraio 2018
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema nervoso
- Malattie del sistema immunitario
- Neoplasie per tipo istologico
- Neoplasie
- Malattie linfoproliferative
- Malattie linfatiche
- Disturbi immunoproliferativi
- Neoplasie per sede
- Linfoma
- Neoplasie del sistema nervoso
- Neoplasie del sistema nervoso centrale
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Inibitori della sintesi degli acidi nucleici
- Inibitori enzimatici
- Agenti antireumatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti Antineoplastici, Alchilanti
- Agenti Alchilanti
- Agenti antineoplastici, immunologici
- Agenti dermatologici
- Agenti di controllo riproduttivo
- Agenti abortivi, non steroidei
- Agenti abortivi
- Antagonisti dell'acido folico
- Temozolomide
- Rituximab
- Metotrexato
Altri numeri di identificazione dello studio
- RTOG-0227
- CDR0000301563
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .