- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00002531
Combination Chemotherapy in Treating Adults With Acute Lymphocytic Leukemia
MULTICENTRE TRIAL OF INTENSIFIED THERAPY FOR ADULT ALL (O5/93)
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Randomized phase II trial to study the effectiveness of various combination chemotherapy regimens in treating patients with acute lymphocytic leukemia.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
- Droga: ciclofosfamide
- Droga: leucovorin calcio
- Radiazione: radioterapia
- Droga: mitoxantrone cloridrato
- Droga: asparaginasi
- Droga: citarabina
- Droga: daunorubicina cloridrato
- Droga: desametasone
- Droga: etoposide
- Droga: metotrexato
- Droga: vincristina solfato
- Procedura: trapianto allogenico di midollo osseo
- Droga: mercaptopurina
- Droga: tioguanina
- Droga: doxorubicina cloridrato
- Procedura: trapianto di cellule staminali del sangue periferico
- Droga: ifosfamide
- Droga: prednisolone
- Droga: vindesina
- Droga: teniposide
Descrizione dettagliata
OBJECTIVES: I. Develop risk-adapted therapy for patients with low-risk, high-risk, T-cell, or B-cell acute lymphocytic leukemia (ALL). II. Determine the complete remission rate in these patients treated with the following strategies: increased doses of cyclophosphamide during induction and reinduction, early use of high-dose cytarabine plus mitoxantrone (for high-risk patients), and increased doses of methotrexate (for B-cell ALL patients). III. Determine the duration of remission and survival of patients in all risk groups treated with intensified consolidation and subtype-specific chemotherapy. IV. Compare the effects of intensified vs conventional maintenance therapy in patients of all risk groups.
OUTLINE: This is a randomized, multicenter study. Patients are assigned to 1 of 4 treatment groups based on disease status. Patients in groups 1-3 with a large leukemic cell mass, in particular those with a WBC greater than 25,000/mm3 and/or marked organomegaly, receive preinduction therapy comprising oral prednisolone (PRDL) 3 times a day on days 1-7 and vincristine (VCR) IV on day 1. Group 1 (low-risk acute lymphocytic leukemia (ALL)): First induction therapy: Patients receive oral PRDL 3 times a day on days 1-7 of weeks 1-4, asparaginase (ASP) IV over 30 minutes on days 1-7 of weeks 3 and 4, VCR IV and daunorubicin IV over 30 minutes on day 1 of weeks 1-4, and methotrexate (MTX) IT on day 1 of week 1. Patients who achieve complete remission (CR) after first induction therapy proceed to first consolidation therapy on group 1. Second induction therapy: Patients receive oral cyclophosphamide (CTX) IV on day 1 of weeks 5, 7, and 9; cytarabine (ARA-C) IV over 1 hour or subcutaneously on days 3-6 and MTX IT on day 3 of weeks 5-8; and oral mercaptopurine (MP) on days 1-7 of weeks 5-8 and day 1 of week 9. Patients who achieve CR during second induction therapy undergo prophylactic cranial irradiation 5 days a week for 2.4 weeks. Patients who achieve CR after second induction therapy proceed to group 3. First consolidation therapy: Patients receive high-dose MTX IV continuously with leucovorin calcium (CF) rescue on day 1, ASP IV over 1 hour on day 2, and oral MP on days 1-5 of weeks 13 and 15; and teniposide (VM-26) IV over 1 hour and ARA-C IV over 1 hour on days 1-5 of week 17. Triple intrathecal therapy (TIT) comprising MTX, ARA-C, and dexamethasone (DM) is also administered on day 1 of week 17. First reinduction therapy: Patients receive oral PRDL three times a day on days 1-7 and VCR IV and doxorubicin (DOX) IV over 30 minutes on day 1 of weeks 21-24, and TIT on day 1 of week 21. Second reinduction therapy: Patients receive CTX IV and TIT on day 1 of week 25, and ARA-C IV over 1 hour on days 3-6 and oral thioguanine (TG) on days 1-7 of weeks 25 and 26. Second consolidation therapy: Patients receive oral MP daily and oral MTX weekly during weeks 29-32, 34-38, 40-44, 46-50, and 52; high-dose MTX, CF rescue, and ASP as in first consolidation therapy during weeks 33 and 45; and VM-26, ARA-C, and TIT as in first consolidation therapy during weeks 39 and 51. Group 2 (T-cell ALL with or without mediastinal involvement): First induction therapy: Patients receive treatment as in first induction therapy on group 1. Patients with residual tumor greater than 2 cm after first induction therapy also undergo mediastinal radiotherapy 5 days a weeks for 2.4-2.7 weeks concurrently with prophylactic cranial irradiation. Second induction therapy: Patients receive treatment as in second induction therapy on group 1. First consolidation therapy: Patients receive high-dose ARA-C IV over 3 hours every 12 hours on days 1-4 and mitoxantrone (DHAD) IV over 30 minutes on days 3-5 during week 13; and high-dose MTX, CF rescue, ASP, and MP as in first consolidation therapy on group 1 during week 17. First reinduction therapy: Patients receive treatment as in first reinduction therapy on group 1. Second reinduction therapy: Patients receive treatment as in second reinduction therapy on group 1. Second consolidation therapy: Patients receive MP and MTX as in second consolidation therapy on group 1; CTX IV, ARA-C IV continuously, and TIT on day 1 during weeks 33 and 45; and VM-26, ARA-C, and TIT as in first consolidation therapy on group 1 during weeks 39 and 51. Group 3 (high-risk ALL): First induction therapy: Patients receive treatment as in first induction therapy on group 1. Second induction therapy: Patients receive CNS-effective chemotherapy comprising high-dose ARA-C every 12 hours on days 1-4 and DHAD IV over 30 minutes on days 3-5 during week 6. First consolidation therapy: Patients receive high-dose MTX, CF rescue, and ASP as in first consolidation therapy on group 1; and CTX, ARA-C, and TIT as in second consolidation therapy on group 2 during week 17. First reinduction therapy: Patients receive treatment as in first reinduction therapy on group 1. Second reinduction therapy: Patients receive treatment as in second reinduction therapy on group 1. Second consolidation therapy: Patients receive MP and MTX as in second consolidation therapy on group 1; treatment as in second induction therapy on group 3 during week 33; high-dose MTX, CF rescue, ASP, and MP as in first consolidation therapy on group 1 during week 39; CTX, ARA-C, and TIT as in second consolidation therapy on group 2 during week 45; and VM-26, ARA-C, and TIT as in first consolidation therapy on group 1 during week 51. Groups 1-3: Patients who are age 15 to 50, achieve first CR, and have a suitable donor undergo allogeneic bone marrow transplantation. Patients who are under age 40 undergo bone marrow transplantation from a matched unrelated donor. Patients who have Philadelphia chromosome/bcr-abl positive disease and no suitable donor undergo purged autologous peripheral blood stem cell transplantation instead of reinduction therapy during first CR. CNS therapy: Patients with CNS disease at entry receive TIT 2 or 3 times weekly beginning immediately upon diagnosis and continuing until 5 doses after blasts are cleared from the CSF. Patients on group 1 and 2 undergo irradiation of the entire neuraxis 5 days a week for 2.7-3.2 weeks during second induction therapy. Maintenance therapy: After completion of 1 year of treatment on group 1, 2, or 3, patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive MP daily and MTX weekly on odd-numbered months between months 13-30; CTX, ARA-C, and TIT as in second consolidation therapy on group 2 during months 14, 20, and 26; VM-26, ARA-C, and TIT as in first consolidation therapy on group 1 during months 16, 22, and 28; and high-dose MTX, CF rescue, and ASP as in first consolidation therapy on group 1 during months 18, 24, and 30. Arm II: Patients receive MP plus MTX as in second consolidation therapy on group 1 continuously and TIT every 2 months during months 13-30. Group 4 (B-cell ALL): Pretreatment: Patients who are age 50 and under receive CTX IV over 1 hour and oral PRDL 3 times a day on days 1-5. Patients who are over age 50 receive CTX IV and oral DM on days 1, 3, and 5. Treatment: Patients receive alternating therapy on blocks A and B. Block A therapy consists of VCR IV, MTX IV continuously, and CF rescue on day 1; ifosfamide IV over 1 hour and oral DM on days 1-5; VM-26 IV over 1 hour and ARA-C IV over 1 hour every 12 hours on days 4 and 5; and TIT on days 1 and 5. Block B therapy consists of VCR IV, MTX IV continuously, and CF rescue on day 1; CTX IV over 1 hour and oral DM on days 1-5; DOX IV over 15 minutes on days 4 and 5; and TIT on days 1 and 5. Blocks A and B continue every 3 weeks for a total of 6 courses. Patients who have not achieved CR after 3 courses or who develop disease progression at any time may optionally receive vindesine, ARA-C, etoposide, and DM. Patients with CNS disease undergo craniospinal irradiation after 2 courses of systemic chemotherapy (block A and B therapy). Patients receive TIT 2-3 times weekly until CSF is clear after block A therapy only if response is unsatisfactory.
PROJECTED ACCRUAL: Approximately 700 patients will be accrued for this study within 4 years.
Tipo di studio
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Frankfurt, Germania, D-60590
- Klinikum der J.W. Goethe Universitaet
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
DISEASE CHARACTERISTICS: Diagnosis of low-risk acute lymphocytic leukemia (ALL) (common ALL or pre-B-cell) Must meet 1 of the following 2 conditions: Age 51 to 65 and meets the following criteria: No mediastinal mass No T-cell or B-cell disease Age 15 to 50 and meets the following criteria: Philadelphia chromosome (Ph) negative bcr-abl negative Initial WBC less than 30,000/mm3 OR Diagnosis of T-cell ALL with or without mediastinal involvement Age 15 to 50 OR Diagnosis of high-risk ALL (common ALL or pre-B-cell) Age 15 to 50 and meets 1 of the following criteria: Ph positive bcr-abl positive Pre-pre-B-cell disease, i.e., t(4;11) Initial WBC greater than 30,000/mm3 OR Diagnosis of B-cell ALL
PATIENT CHARACTERISTICS: Age: See Disease Characteristics 15 to 65 Performance status: Not specified Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: No renal failure Cardiovascular: No cardiomyopathy Other: HIV-1 and HIV-2 negative No severe psychiatric disease
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior cytostatic drugs except vincristine Endocrine therapy: Prior corticosteroids allowed Radiotherapy: Not specified Surgery: Not specified Other: No more than 2 weeks of prior therapy No other prior cytostatic drugs
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
Collaboratori e investigatori
Investigatori
- Cattedra di studio: Dieter Hoelzer, MD, PhD, Johann Wolfgang Goethe University Hospital
Pubblicazioni e link utili
Pubblicazioni generali
- Bruggemann M, Raff T, Flohr T, Gokbuget N, Nakao M, Droese J, Luschen S, Pott C, Ritgen M, Scheuring U, Horst HA, Thiel E, Hoelzer D, Bartram CR, Kneba M; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006 Feb 1;107(3):1116-23. doi: 10.1182/blood-2005-07-2708. Epub 2005 Sep 29.
- Burmeister T, Goekbuget N, Schwartz S, et al.: Outcome of adult ALL patients with fusion transcript E2A-PBX1: results from the GMALL therapy trials 5/93 and 6/99. [Abstract] Blood 108 (11): A-1888, 2006.
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Studia le date principali
Inizio studio
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Neoplasie per tipo istologico
- Neoplasie
- Leucemia
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti autonomi
- Agenti del sistema nervoso periferico
- Agenti antivirali
- Inibitori della sintesi degli acidi nucleici
- Inibitori enzimatici
- Analgesici
- Agenti del sistema sensoriale
- Agenti antinfiammatori
- Agenti antireumatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Modulatori della tubulina
- Agenti antimitotici
- Modulatori della mitosi
- Antiemetici
- Agenti gastrointestinali
- Glucocorticoidi
- Ormoni
- Ormoni, sostituti ormonali e antagonisti ormonali
- Agenti antineoplastici, ormonali
- Agenti protettivi
- Agenti Antineoplastici, Alchilanti
- Agenti Alchilanti
- Agonisti mieloablativi
- Agenti antineoplastici, fitogenici
- Inibitori della topoisomerasi II
- Inibitori della topoisomerasi
- Agenti dermatologici
- Micronutrienti
- Antibiotici, Antineoplastici
- Vitamine
- Agenti di controllo riproduttivo
- Antidoti
- Complesso di vitamina B
- Agenti abortivi, non steroidei
- Agenti abortivi
- Antagonisti dell'acido folico
- Desametasone
- Prednisolone
- Ciclofosfamide
- Etoposide
- Ifosfamide
- Leucovorin
- Levoleucovorin
- Doxorubicina
- Doxorubicina liposomiale
- Citarabina
- Metotrexato
- Vincristina
- Daunorubicina
- Asparaginasi
- Mitoxantrone
- Mercaptopurina
- Tioguanina
- Vindesine
- Teniposide
Altri numeri di identificazione dello studio
- CDR0000078421
- GER-GMALL-ALL-05/93
- EU-93002
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 .