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

1 luglio 2016 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

47

Fase

  • Fase 2

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

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

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

  • Bambino
  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

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: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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)
Biologico: 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)
Altri nomi:
  • G-CSF
Biologico: 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
Droga: cytarabine
2 g/sq m IV infusion over 2 hours q 12 hrs x 8 doses Days 1-4 of Cycle 6
Droga: etoposide
5 mg/kg IV infusion over 12 hrs q 12 hrs x 8 doses Days 1-4 of Cycle 6
Droga: 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.
Droga: 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.
Droga: temozolomide
150 mg/sq m PO Days 7-11 Cycles 1-5.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Complete Response Rate After Remission Induction
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
4 Year Progression Free Rate
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Alliance for Clinical Trials in Oncology

Collaboratori

National Cancer Institute (NCI)

Investigatori

  • Cattedra di studio: James Rubenstein, MD, PhD, University of California, San Francisco

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.

Pubblicazioni generali

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 ottobre 2004

Completamento primario (Effettivo)

1 gennaio 2010

Completamento dello studio (Effettivo)

1 settembre 2014

Date di iscrizione allo studio

Primo inviato

8 dicembre 2004

Primo inviato che soddisfa i criteri di controllo qualità

8 dicembre 2004

Primo Inserito (Stima)

9 dicembre 2004

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

6 luglio 2016

Ultimo aggiornamento inviato che soddisfa i criteri QC

1 luglio 2016

Ultimo verificato

1 luglio 2016

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • CALGB-50202
  • U10CA031946 (Sovvenzione/contratto NIH degli Stati Uniti)
  • CDR0000398106 (Identificatore di registro: NCI Physician Data Query)

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 .

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