Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia
Information source: University of Schleswig-Holstein
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: asparaginase (Drug); cyclophosphamide (Drug); cytarabine (Drug); daunorubicin hydrochloride (Drug); dexamethasone (Drug); doxorubicin hydrochloride (Drug); etoposide (Drug); ifosfamide (Drug); mercaptopurine (Drug); methotrexate (Drug); prednisone (Drug); thioguanine (Drug); vincristine sulfate (Drug); vindesine (Drug); radiation therapy (Radiation)
Phase: Phase 3
Status: Completed
Sponsored by: University of Schleswig-Holstein Official(s) and/or principal investigator(s): Martin Schrappe, MD, PhD, Study Chair, Affiliation: University of Schleswig-Holstein
Summary
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. Giving more than one
drug (combination chemotherapy) may kill more cancer cells. It is not yet known which
combination chemotherapy regimen is more effective in treating young patients with acute
lymphoblastic leukemia.
PURPOSE: Thisphase III trial is studying several different combination chemotherapy regimens
to compare how well they work in treating young patients with acute lymphoblastic leukemia.
Clinical Details
Official title: ALL-BFM 2000 Multi-Center Study for the Treatment of Children and Adolescents With Acute Lymphoblastic Leukemia
Study design: Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Efficacy of dexamethasone vs prednisone during the induction phaseEvent-free survival (EFS) and overall survival after initial remission in intermediate-risk and high-risk patients Safety and efficacy of treatment reduction during reintensification in standard-risk patients EFS after second delayed reintensification in intermediate-risk patients Outcome after extended reintensification therapy in high-risk patients
Detailed description:
OBJECTIVES:
- Compare the relative efficacy of induction therapy comprising dexamethasone or
prednisone, in terms of a higher rate of event-free survival (EFS) and overall survival
and a reduced rate of relapse, in pediatric patients with intermediate-risk or
high-risk acute lymphoblastic leukemia (ALL).
- Compare the relative safety of a reduced-intensity reintensification regimen comprising
dexamethasone, vincristine, cyclophosphamide, and anthracyclines vs a standard
treatment regimen in pediatric patients with standard-risk ALL identified by fast
clearance of leukemic cells.
- Compare the efficacy of a second delayed reintensification regimen vs standard
reintensification therapy, in terms of improved EFS, in pediatric patients with
intermediate-risk ALL.
- Compare the efficacy of extended reintensification therapy (triple reinduction) vs
standard reintensification therapy (intensive pulses and one reintensification) in
pediatric patients with high-risk ALL.
OUTLINE: This is a randomized, multicenter study.
- Prednisone prephase therapy: Patients receive oral prednisone on days 1-7 and one dose
of methotrexate (MTX) intrathecally (IT) on day 1.
- Induction/consolidation therapy, protocol I: Patients are randomized to 1 of 2
treatment arms.
- Arm I (closed to accrual as of 6/30/2006): Patients receive prednisone (PRED) on
days 8-28.
- Arm II (closed to accrual as of 6/30/2006): Patients receive dexamethasone (DEXA)
on days 8-28.
Patients in both arms also receive vincristine (VCR) and daunorubicin hydrochloride (DNR)
once weekly in weeks 2-5; asparaginase (ASP) on days 12-33; cyclophosphamide (CPM) on days
36 and 64; cytarabine (ARA-C) in weeks 6-9; mercaptopurine (MP) on days 36-63; and MTX IT on
days 1, 12, 33, 45, and 59.*
NOTE: *Patients with CNS disease also receive MTX IT on days 18 and 27.
After completion of induction/consolidation therapy, patients are stratified according to
risk group based on disease response (standard-risk [SR] group [negative minimal residual
disease (MRD) on day 33 and before protocol M, day 78] vs high-risk [HR] group [MRD ≥ 10^-³
on day 78] vs intermediate-risk [IR] group [all nonSR/nonHR]).* Patients with SR and IR
disease proceed to extracompartment therapy. Patients with HR disease proceed to
reintensification therapy.
NOTE: *Patients meeting any of the following criteria are placed in the HR group regardless
of MRD response: Philadelphia chromosome-positive disease (BCR/ABL or t[9;22];
translocations [t4;11][q11;q23] or MLL/AF4); "prednisone-poor-response" (≥ 1,000 blasts/mm³
in the peripheral blood on day 8 after prednisone prephase therapy); or no response to study
induction therapy (M2/3 at day 33).
- Extracompartment therapy, protocol M: Patients receive MP on days 1-56 and MTX on days
8, 22, 36, and 50.
After completion of extracompartment therapy, SR and IR patients proceed to
reintensification therapy. SR patients are randomized to arms I or II. IR patients are
randomized to arms I or III. HR patients who have completed induction/consolidation therapy
are randomized to arms IV or V.
- Reintensification therapy:
- Arm I (standard reinduction therapy, protocol II [closed to accrual as of
6/30/2006]): SR and IR patients receive DEXA on days 1-22; VCR and doxorubicin
hydrochloride (DOX) in weeks 2-5; ASP on days 8, 11, 15, and 18; CPM on day 36;
ARA-C and thioguanine (TG) on days 36-49; and MTX IT on days 38 and 45.* Patients
then proceed to maintenance therapy.
NOTE: *Patients with CNS disease also receive MTX IT on days 1 and 18.
- Arm II (reduced-intensity reinduction therapy, protocol III [closed to accrual as of
6/30/2006]): SR patients receive DEXA on days 1-15; VCR and DOX on days 1 and 8; ASP on
days 1, 4, 8, and 11; CPM on day 15; ARA-C and TG on days 15-28; and MTX IT on days 17
and 24.* Patients then proceed to maintenance therapy.
NOTE: *Patients with CNS disease also receive MTX on day 1.
- Arm III (reduced-intensity reinduction/second delayed reinduction therapy [double
reintensification therapy] [closed to accrual as of 6/30/2006]): IR patients receive
reduced-intensity reintensification therapy as in arm II. After a 10-week interim
maintenance phase, treatment repeats once for a second delayed course of
reintensification therapy. Patients then proceed to maintenance therapy.
- Arm IV (standard reintensification therapy [closed to accrual as of 6/30/2006]): HR
patients receive two sequences of the following HR therapy elements (i. e., in this
order: 1, 2, 3, 1, 2, 3) following reintensification therapy as in arm I. Patients then
proceed to maintenance therapy.
- Element HR-1: Patients receive DEXA on days 1-5; VCR on days 1 and 6; ARA-C twice
on day 5; MTX and CPM every 12 hours on days 2-4 (5 doses); ASP on days 6 and 11;
and MTX/ARA-C/PRED IT on day 1.
- Element HR-2: Patients receive DEXA on days 1-5; vindesine on days 1 and 6; DNR on
day 5; MTX and ifosfamide every 12 hours on days 2-4 (5 doses); ASP on days 6 and
11; and MTX/ARA-C/PRED IT on day 1.* NOTE: *HR patients with CNS disease also
receive IT therapy on day 5.
- Element HR-3: Patients receive DEXA on days 1-5; ARA-C every 12 hours on days 1-2
(4 doses); etoposide five times daily on days 3-5; ASP on days 6 and 11; and
MTX/ARA-C/PRED IT on day 1.
- Arm V (extended reintensification therapy [triple protocol III] [closed to accrual as
of 6/30/2006]): HR patients receive HR therapy elements 3, 2, and 1 as in arm IV
following reintensification therapy as in arm II repeated the therapy element twice
with 4-week interim maintenance phases in between. Patients then proceed to maintenance
therapy.
- Interim maintenance/maintenance therapy: Patients receive MTX once weekly and MP
daily until week 104.
- Radiotherapy: HR patients or patients with T-cell acute lymphoblastic leukemia or
CNS disease undergo CNS radiotherapy.
PROJECTED ACCRUAL: A total of 2,000 patients will be accrued for this study.
Eligibility
Minimum age: 1 Year.
Maximum age: 18 Years.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Histologically confirmed acute lymphoblastic leukemia (ALL)
- No secondary ALL
PATIENT CHARACTERISTICS:
- No prior disease that would preclude treatment with chemotherapy
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior chemotherapy
- More than 4 weeks since prior steroids
Locations and Contacts
Krankenhaus Dornbirn, Dornbirn A-6850, Austria
Landeskrankenhaus Feldkirch, Feldkirch-Tisis A-6807, Austria
Universitaet Kinderklinik, Graz 8036, Austria
Innsbruck Universitaetsklinik, Innsbruck A-6020, Austria
Landeskrankenhaus Klagenfurt, Klagenfurt 9026, Austria
LKH Leoben, Leoben A-8700, Austria
A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung, Linz 4010, Austria
Landes-Kinderkrankenhaus, Linz A-4020, Austria
St. Johanns-Spital, Salzburg A-5020, Austria
St. Anna Children's Hospital, Vienna A-1090, Austria
Kinderklinik - Universitaetsklinikum Aachen, Aachen D-52074, Germany
Klinikum Augsburg, Augsburg DOH-86156, Germany
Caritas-Krankenhaus Bad Mergentheim, Bad Mergentheim D-97980, Germany
Klinikum Bayreuth, Bayreuth D-95445, Germany
Charite University Hospital - Campus Virchow Klinikum, Berlin D-13353, Germany
Helios Klinikum Berlin, Berlin 13125, Germany
Kinderklinik der Universitaet Bonn, Bonn D-53113, Germany
Staedtisches Klinikum - Howedestrase, Braunschweig 38118, Germany
Klinikum Chemnitz gGmbH, Chemnitz D-09116, Germany
Klinikum Coburg, Coburg 96450, Germany
Children's Hospital, Cologne D-50924, Germany
Kliniken der Stadt Koeln gGmbH - Kinderkrankenhaus Riehl, Cologne D-50735, Germany
Carl - Thiem - Klinkum Cottbus, Cottbus D-03048, Germany
Vestische Kinderklinik Universitaetsklinik Witten/Herdecke, Datteln 45711, Germany
Klinikum Lippe - Detmold, Detmold D-32756, Germany
Klinikum Dortmund, Dortmund D-44137, Germany
Universitatsklinikum Carl Gustav Carus, Dresden D-01307, Germany
Klinikum Duisburg, Duisburg D-47055, Germany
Helios Klinikum Erfurt, Erfurt 99089, Germany
Universitaets - Kinderklinik, Erlangen 91054, Germany
Universitaetsklinikum Essen, Essen D-45147, Germany
Klinikum der J.W. Goethe Universitaet, Frankfurt D-60590, Germany
Universitaetskinderklinik - Universitaetsklinikum Freiburg, Freiburg D-79106, Germany
Kinderklinik, Giessen D-35385, Germany
Universitaetsklinikum Goettingen, Goettingen D-37075, Germany
Universitaetsklinikum Halle, Halle D-06097, Germany
Medizinische Hochschule Hannover, Hannover D-30625, Germany
Universitaets-Kinderklinik Heidelberg, Heidelberg D-69120, Germany
SLK - Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen, Heilbronn D-74064, Germany
Gemeinschaftskrankenhaus, Herdecke 58313, Germany
Universitaetsklinikum des Saarlandes, Homburg 66421, Germany
Universitaets - Kinderklinik, Jena D-07745, Germany
Staedtisches Klinikum Karlsruhe gGmbH, Karlsruhe 76133, Germany
Klinikum Kassel, Kassel D-34125, Germany
University Hospital Schleswig-Holstein - Kiel Campus, Kiel D-24105, Germany
Klinikum Kemperhof Koblenz, Koblenz D-56065, Germany
St. Annastift Krankenhaus, Ludwigshafen 67065, Germany
Universitaets - Kinderklinik - Luebeck, Luebeck D-23538, Germany
Universitatsklinikum der MA, Magdeburg 39120, Germany
Staedtisches Klinik - Kinderklinik, Mannheim D-68167, Germany
Universitaetsklinikum Giessen und Marburg GmbH - Marburg, Marburg D-35043, Germany
Klinikum Minden, Minden D-32423, Germany
Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster, Muenster D-48149, Germany
Krankenhaus Muenchen Schwabing, Munich 80804, Germany
Kinderklinik Kohlhof, Neunkirchen D-66539, Germany
Cnopf'sche Kinderklinik, Nuremberg 90419, Germany
Klinikum Oldenburg, Oldenburg 26133, Germany
Kinderklinik - Universitaetsklinikum Rostock, Rostock D-18057, Germany
Saarbrucker Winterbergkliniken, Saarbrucken 66119, Germany
Klinikum Schwerin, Schwerin D-19049, Germany
Kinderklink Siegen Deutsches Rotes Kreuz, Siegen D-57072, Germany
Johanniter-Kinderklinik, St. Augustin 53757, Germany
Olgahospital, Stuttgart D-70176, Germany
Krankenanstalt Mutterhaus der Borromaerinnen, Trier D-54290, Germany
Universitaetsklinikum Tuebingen, Tuebingen D-72076, Germany
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm, Ulm D-89075, Germany
St. Marienhospital - Vechta, Vechta D-49377, Germany
Reinhard-Nieter-Krankenhaus, Wilhelmshaven D-26389, Germany
Klinikum der Stadt Wolfsburg, Wolfsburg D-38440, Germany
Universitaets - Kinderklinik Wuerzburg, Wuerzburg D-97080, Germany
Kantonsspital Aarau, Aarau CH-5001, Switzerland
Universitaets-Kinderspital beider Basel, Basel CH-4005, Switzerland
Ospedale "la Carita", Locarno, Locarno 6600, Switzerland
Kinderspital Luzern, Lucerne 16 CH-6000, Switzerland
Ostschweizer Kinderspital, St. Gallen CH-9006, Switzerland
University Children's Hospital, Zurich CH-8032, Switzerland
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Related publications: Attarbaschi A, Mann G, Panzer-Grümayer R, Röttgers S, Steiner M, König M, Csinady E, Dworzak MN, Seidel M, Janousek D, Möricke A, Reichelt C, Harbott J, Schrappe M, Gadner H, Haas OA. Minimal residual disease values discriminate between low and high relapse risk in children with B-cell precursor acute lymphoblastic leukemia and an intrachromosomal amplification of chromosome 21: the Austrian and German acute lymphoblastic leukemia Berlin-Frankfurt-Munster (ALL-BFM) trials. J Clin Oncol. 2008 Jun 20;26(18):3046-50. doi: 10.1200/JCO.2008.16.1117.
Starting date: July 2000
Last updated: May 28, 2013
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