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Chemotherapy, Imatinib Mesylate, and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

13 novembre 2014 aggiornato da: National Cancer Institute (NCI)

A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC # 716051), and Transplantation for Adults With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by the CALGB and SWOG

This phase II trial studies how well giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation works in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

PRIMARY OBJECTIVES:

I. Determine the activity of imatinib mesylate (Gleevec) to prolong disease-free survival (DFS) and overall survival in acute lymphoblastic leukemia (ALL) patients with t(9;22).

II. Determine the ability of imatinib mesylate (Gleevec) to produce or maintain a BCR-ABL-negative status, as judged by real-time-polymerase chain reaction (RT-PCR) following sequential chemotherapy, imatinib mesylate (Gleevec) and transplantation.

III. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous transplantation following imatinib mesylate (Gleevec) therapy.

IV. Study the safety and efficacy of autologous peripheral stem cell transplantation following therapy with imatinib mesylate (Gleevec).

V. Study the safety and efficacy of allogeneic stem cell transplantation following therapy with imatinib mesylate (Gleevec).

VI. Study the safety and efficacy of imatinib mesylate (Gleevec) administered after allogeneic or autologous stem cell transplant.

OUTLINE:

COURSE I (remission induction): Patients receive 1 course of front-line induction therapy on a Cancer and Leukemia Group B (CALGB)/Southwest Oncology Group (SWOG) protocol prior to enrollment.

COURSE II (imatinib mesylate): Patients receive imatinib mesylate orally (PO) twice daily on days 1-28.

COURSE III (CNS prophylaxis): Within 7 days after completing course II, patients receive methotrexate intrathecally (IT), methotrexate intravenously (IV) over 3 hours, and vincristine sulfate IV on days 1, 8, and 15; methotrexate PO every 6 hours on days 1-2, 8-9, and 15-16; leucovorin calcium IV on days 2, 9, and 16; and leucovorin calcium PO every 6 hours on days 3, 4, 10, 11, 17, and 18.

COURSE IV (imatinib mesylate): After blood counts recover after completion of course III, patients receive imatinib mesylate as in course II.

COURSE V: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT), autologous PBSCT, or no PBSCT.

COURSE Va (allogeneic PBSCT for patients with human leukocyte antigen [HLA]-matched sibling donor): Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.

COURSE Vb (autologous PBSCT for patients without HLA-matched sibling donor): Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive filgrastim SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive filgrastim SC beginning on day 0 and continuing until blood counts recover.

COURSE Vc (no transplantation for patients who are not transplant candidates): Beginning 3-10 days after completion of course IV, patients who are not candidates for PBSCT receive etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive filgrastim SC once or twice a day beginning on day 14 and continuing until blood counts recover.

COURSE VI: Patients receive imatinib mesylate PO once or twice daily beginning on day 30 post transplantation or on day 30 if no transplantation received and continuing for at least 1 year or until patient has 2 consecutive negative reverse transcriptase-polymerase chain reaction assays at least 3 months apart or until relapse.

After completion of study treatment, patients are followed up monthly for 1 year, every 3 months for 2 years, every 6 months for 2 years, then yearly for 5 years.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

58

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
    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30342
        • Blood and Marrow Transplant Group of Georgia
    • Illinois
      • Bloomington, Illinois, Stati Uniti, 61701
        • Saint Joseph Medical Center
      • Canton, Illinois, Stati Uniti, 61520
        • Graham Hospital Association
      • Carthage, Illinois, Stati Uniti, 62321
        • Memorial Hospital
      • Chicago, Illinois, Stati Uniti, 60637
        • University of Chicago
      • Chicago, Illinois, Stati Uniti, 60640
        • Weiss Memorial Hospital
      • Eureka, Illinois, Stati Uniti, 61530
        • Eureka Hospital
      • Galesburg, Illinois, Stati Uniti, 61401
        • Galesburg Cottage Hospital
      • Galesburg, Illinois, Stati Uniti, 61401
        • Illinois CancerCare Galesburg
      • Havana, Illinois, Stati Uniti, 62644
        • Mason District Hospital
      • Hopedale, Illinois, Stati Uniti, 61747
        • Hopedale Medical Complex - Hospital
      • Macomb, Illinois, Stati Uniti, 61455
        • Mcdonough District Hospital
      • Maywood, Illinois, Stati Uniti, 60153
        • Loyola University Medical Center
      • Normal, Illinois, Stati Uniti, 61761
        • Community Cancer Center Foundation
      • Normal, Illinois, Stati Uniti, 61761
        • Bromenn Regional Medical Center
      • Ottawa, Illinois, Stati Uniti, 61350
        • Illinois CancerCare-Ottawa Clinic
      • Ottawa, Illinois, Stati Uniti, 61350
        • Ottawa Regional Hospital and Healthcare Center
      • Pekin, Illinois, Stati Uniti, 61554
        • Pekin Cancer Treatment Center
      • Pekin, Illinois, Stati Uniti, 61554
        • Pekin Hospital
      • Peoria, Illinois, Stati Uniti, 61637
        • OSF Saint Francis Medical Center
      • Peoria, Illinois, Stati Uniti, 61615
        • Illinois CancerCare-Peoria
      • Peoria, Illinois, Stati Uniti, 61614
        • Proctor Hospital
      • Peoria, Illinois, Stati Uniti, 61603
        • Methodist Medical Center of Illinois
      • Peoria, Illinois, Stati Uniti, 61615
        • Illinois Oncology Research Association CCOP
      • Peru, Illinois, Stati Uniti, 61354
        • Illinois Valley Hospital
      • Princeton, Illinois, Stati Uniti, 61356
        • Perry Memorial Hospital
      • Spring Valley, Illinois, Stati Uniti, 61362
        • Saint Margaret's Hospital
    • Indiana
      • Fort Wayne, Indiana, Stati Uniti, 46845
        • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • Kansas
      • Chanute, Kansas, Stati Uniti, 66720
        • Cancer Center of Kansas - Chanute
      • Dodge City, Kansas, Stati Uniti, 67801
        • Cancer Center of Kansas - Dodge City
      • El Dorado, Kansas, Stati Uniti, 67042
        • Cancer Center of Kansas - El Dorado
      • Kansas City, Kansas, Stati Uniti, 66112
        • Providence Medical Center
      • Kingman, Kansas, Stati Uniti, 67068
        • Cancer Center of Kansas-Kingman
      • Lawrence, Kansas, Stati Uniti, 66044
        • Lawrence Memorial Hospital
      • Newton, Kansas, Stati Uniti, 67114
        • Cancer Center of Kansas - Newton
      • Olathe, Kansas, Stati Uniti, 66061
        • Radiation Oncology Center of Olathe
      • Overland Park, Kansas, Stati Uniti, 66210
        • Radiation Oncology Practice Corporation Southwest
      • Parsons, Kansas, Stati Uniti, 67357
        • Cancer Center of Kansas - Parsons
      • Pratt, Kansas, Stati Uniti, 67124
        • Cancer Center of Kansas - Pratt
      • Salina, Kansas, Stati Uniti, 67401
        • Salina Regional Health Center
      • Salina, Kansas, Stati Uniti, 67401
        • Cancer Center of Kansas - Salina
      • Wellington, Kansas, Stati Uniti, 67152
        • Cancer Center of Kansas - Wellington
      • Wichita, Kansas, Stati Uniti, 67208
        • Cancer Center of Kansas-Wichita Medical Arts Tower
      • Wichita, Kansas, Stati Uniti, 67208
        • Associates In Womens Health
      • Wichita, Kansas, Stati Uniti, 67214
        • Cancer Center of Kansas - Main Office
      • Wichita, Kansas, Stati Uniti, 67214
        • Via Christi Regional Medical Center
      • Wichita, Kansas, Stati Uniti, 67214
        • Wichita CCOP
      • Winfield, Kansas, Stati Uniti, 67156
        • Cancer Center of Kansas - Winfield
    • Maine
      • Bangor, Maine, Stati Uniti, 04401
        • Eastern Maine Medical Center
    • Massachusetts
      • Beverly, Massachusetts, Stati Uniti, 01915
        • Beverly Hospital
      • Gloucester, Massachusetts, Stati Uniti, 01930
        • Addison Gilbert Hospital
      • Worcester, Massachusetts, Stati Uniti, 01605
        • Commonwealth Hematology Oncology PC-Worcester
    • Missouri
      • Independence, Missouri, Stati Uniti, 64057
        • Centerpoint Medical Center LLC
      • Kansas City, Missouri, Stati Uniti, 64111
        • Saint Luke's Cancer Institute
      • Kansas City, Missouri, Stati Uniti, 64114
        • Radiation Oncology Practice Corporation South
      • Kansas City, Missouri, Stati Uniti, 64154
        • Radiation Oncology Practice Corporation - North
      • Liberty, Missouri, Stati Uniti, 64068
        • Liberty Hospital
      • Saint Louis, Missouri, Stati Uniti, 63110
        • Washington University School of Medicine
    • Montana
      • Billings, Montana, Stati Uniti, 59101
        • Saint Vincent Healthcare
      • Billings, Montana, Stati Uniti, 59101
        • Northern Rockies Radiation Oncology Center
      • Billings, Montana, Stati Uniti, 59101
        • Montana Cancer Consortium CCOP
      • Billings, Montana, Stati Uniti, 59102
        • Hematology-Oncology Centers of the Northern Rockies PC
      • Billings, Montana, Stati Uniti, 59107-7000
        • Billings Clinic
      • Billings, Montana, Stati Uniti, 59107
        • Deaconess Medical Center
      • Bozeman, Montana, Stati Uniti, 59715
        • Bozeman Deaconess Hospital
      • Bozeman, Montana, Stati Uniti, 59715
        • Bozeman Deaconess Cancer Center
      • Bozeman, Montana, Stati Uniti, 59715
        • Internal Medicine of Bozeman
      • Butte, Montana, Stati Uniti, 59701
        • Saint James Community Hospital and Cancer Treatment Center
      • Great Falls, Montana, Stati Uniti, 59405
        • Great Falls Clinic
      • Great Falls, Montana, Stati Uniti, 59405
        • Berdeaux, Donald MD (UIA Investigator)
      • Helena, Montana, Stati Uniti, 59601
        • Saint Peter's Community Hospital
      • Kalispell, Montana, Stati Uniti, 59901
        • Kalispell Regional Medical Center
      • Kalispell, Montana, Stati Uniti, 59901
        • Glacier Oncology PLLC
      • Kalispell, Montana, Stati Uniti, 59901
        • Kalispell Medical Oncology
      • Missoula, Montana, Stati Uniti, 59802
        • Saint Patrick Hospital - Community Hospital
      • Missoula, Montana, Stati Uniti, 59804
        • Guardian Oncology and Center for Wellness
      • Missoula, Montana, Stati Uniti, 59801
        • Community Medical Hospital
      • Missoula, Montana, Stati Uniti, 59802
        • Montana Cancer Specialists
    • New Hampshire
      • Keene, New Hampshire, Stati Uniti, 03431
        • Cheshire Medical Center-Dartmouth-Hitchcock Keene
      • Rochester, New Hampshire, Stati Uniti, 03867
        • Frisbie Hospital
    • New York
      • Buffalo, New York, Stati Uniti, 14263
        • Roswell Park Cancer Institute
      • Manhasset, New York, Stati Uniti, 11030
        • North Shore University Hospital
      • Manhasset, New York, Stati Uniti, 11030
        • North Shore-LIJ Health System CCOP
      • New Hyde Park, New York, Stati Uniti, 11040
        • Long Island Jewish Medical Center
      • New Hyde Park, New York, Stati Uniti, 11040
        • North Shore-LIJ Health System/Center for Advanced Medicine
      • New York, New York, Stati Uniti, 10065
        • Weill Medical College of Cornell University
      • Oswego, New York, Stati Uniti, 13126
        • Oswego Hospital
      • Rochester, New York, Stati Uniti, 14642
        • University of Rochester
      • Syracuse, New York, Stati Uniti, 13210
        • State University of New York Upstate Medical University
    • North Carolina
      • Kinston, North Carolina, Stati Uniti, 28501
        • Kinston Medical Specialists PA
      • Winston-Salem, North Carolina, Stati Uniti, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Columbus, Ohio, Stati Uniti, 43210
        • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Stati Uniti, 15224-1791
        • Western Pennsylvania Hospital
    • South Carolina
      • Charleston, South Carolina, Stati Uniti, 29425
        • Medical University of South Carolina
    • Vermont
      • St. Johnsbury, Vermont, Stati Uniti, 05819
        • Northeastern
    • Virginia
      • Richmond, Virginia, Stati Uniti, 23298
        • Virginia Commonwealth University
    • Wyoming
      • Sheridan, Wyoming, Stati Uniti, 82801
        • Welch Cancer 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

Da 15 anni a 59 anni (Bambino, Adulto)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Unequivocal histologic diagnosis of ALL
  • Detection of the t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics or BCR-ABL positive by molecular analysis (RT-PCR or fluorescence in situ hybridization [FISH})

  • Prior Therapy:

    • Complete or partial remission following one course of induction chemotherapy with an intensive 4 or 5 drug regimen (with or without imatinib mesylate) on a CALGB or SWOG ALL protocol for previously untreated ALL patients

      • Note: The double induction regimen of SWOG S0333 is considered to be one course of induction chemotherapy for the purpose of this eligibility criterion; therefore, patients from S0333 may be eligible for this study only after completing the entire double induction regimen

    • Complete or partial remission following one course of therapy on any standard induction regimen (with or without imatinib mesylate) without prior enrollment on a cooperative group frontline protocol; in these instances, documentation of Philadelphia chromosome (Ph)+ positivity may occur outside a CALGB or SWOG laboratory

      • Note: CALGB institutions must enroll patients on CALGB 9862 and submission of an initial sample for the companion trial must occur at time of enrollment on CALGB C10001; enrollment on companion studies CALGB 8461 and 9665 is not required
  • No more than six weeks of prior imatinib mesylate during induction therapy before study enrollment
  • Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control and contraception should continue for three months after the last dose of imatinib mesylate (Gleevec) to allow complete clearance of drug and its principle metabolites from the body; in women of childbearing potential, a pregnancy test will be required at study entry

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: Treatment (imatinib mesylate, chemotherapy, PBSCT)
See Detailed Description.
Altro: analisi di laboratorio dei biomarcatori
Studi correlati
Droga: ciclofosfamide
Dato IV
Altri nomi:
  • Cytoxan
  • Endossano
  • CPM
  • CTX
  • Endoxana
Droga: etoposide
Dato IV
Altri nomi:
  • EPEG
  • VP-16
  • VP-16-213
Droga: citarabina
Dato IV
Altri nomi:
  • Cytosar-U
  • citosina arabinoside
  • ARA-C
  • arabinofuranosilcitosina
  • arabinosilcitosina
Droga: vincristina solfato
Dato IV
Altri nomi:
  • Videoregistratore
  • leurocristina solfato
  • Vincasar PFS
Biologico: filgrastim
Dato SC
Altri nomi:
  • G-CSF
  • Neupogen
Radiazione: irradiazione totale del corpo
Sottoponiti a trauma cranico
Altri nomi:
  • Trauma cranico
Droga: tacrolim
Dato IV o PO
Altri nomi:
  • Prograf
  • FK 506
Procedura: trapianto allogenico di cellule staminali emopoietiche
Sottoponiti a PBSCT allogenico
Procedura: trapianto di cellule staminali del sangue periferico
Sottoponiti a PBSCT
Altri nomi:
  • Trapianto di PBPC
  • Trapianto di PBSC
  • trapianto di cellule progenitrici del sangue periferico
  • trapianto, cellule staminali del sangue periferico
Procedura: trapianto autologo di cellule staminali emopoietiche
Sottoponiti a PBSCT autologo
Droga: imatinib mesilato
Dato PO
Altri nomi:
  • Gleevec
  • CGP 57148
  • Glivec
Droga: leucovorin calcio
Dato IV e PO
Altri nomi:
  • Cf
  • CFR
  • LV
Droga: methotrexate
Given IT and IV
Altri nomi:
  • amethopterina
  • Folex
  • metilamminopterina
  • Mexato
  • MTX

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Disease Free Survival
Lasso di tempo: Duration of treatment (up to 10 years)

Disease-free survival (DFS) was measured as the interval from achievement of complete remission (CR) until relapse or death, regardless of cause; patients alive and in CR were censored at last follow-up. DFS was estimated using the Kaplan Meier method.

A complete remission (CR) was defined as recovery of morphologically normal bone marrow and blood counts (i.e., neutrophils >= 1.5 x 10^9/L and platelets > 100 x 10^9/L) and no circulating leukemic blasts or evidence of extramedullary leukemia and persisting for at least one month.
Duration of treatment (up to 10 years)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Sopravvivenza globale
Lasso di tempo: Durata dello studio (fino a 10 anni)
Sopravvivenza globale (OS) come intervallo dalla data in studio fino al decesso. L'OS è stata stimata utilizzando il metodo Kaplan Meier.
Durata dello studio (fino a 10 anni)
Number of Participants Who Achieved a BCR-ABL Response at 12 Months
Lasso di tempo: 12 months

BCR-ABL response is defined in two ways: complete molecular response (CMR) and major molecular response (MMR).

Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene

MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally).
12 months
5 Year Disease-free Survival for Autologous & Allogeneic Transplant Groups
Lasso di tempo: 5 years from CR
Percentage of patients who achieved a complete remission (CR) and were alive and relapse free at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.
5 years from CR
5 Year Overall Survival for Autologous & Allogeneic Transplant Groups
Lasso di tempo: 5 years from registration
Percentage of patients who were alive at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.
5 years from registration

Collaboratori e investigatori

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

Sponsor

National Cancer Institute (NCI)

Investigatori

  • Investigatore principale: Meir Wetzler, Cancer and Leukemia Group B

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 aprile 2002

Completamento primario (Effettivo)

1 aprile 2012

Completamento dello studio (Effettivo)

1 febbraio 2014

Date di iscrizione allo studio

Primo inviato

6 giugno 2002

Primo inviato che soddisfa i criteri di controllo qualità

26 gennaio 2003

Primo Inserito (Stima)

27 gennaio 2003

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

24 novembre 2014

Ultimo aggiornamento inviato che soddisfa i criteri QC

13 novembre 2014

Ultimo verificato

1 giugno 2014

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • NCI-2009-00436 (Identificatore di registro: CTRP (Clinical Trial Reporting Program))
  • U10CA031946 (Sovvenzione/contratto NIH degli Stati Uniti)
  • CDR0000069378
  • CALGB 10001/SWOG C10001 (Altro identificatore: Cancer and Leukemia Group B)
  • CALGB-10001 (Altro identificatore: CTEP)

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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