RATIONALE: Giving combination chemotherapy and total-body irradiation before a peripheral
stem cell transplant that uses the patient's or a donor's stem cells, helps stop both the
growth of cancer cells and the patient's immune system from rejecting the stem cells. When
the stem cells are infused into the patient they may help the patient's bone marrow make
stem cells, red blood cells, white blood cells, and platelets. Giving combination
chemotherapy and total-body irradiation followed by a stem cell transplant may be an
effective treatment for anaplastic large cell lymphoma.
PURPOSE: This clinical trial is studying how well combination chemotherapy followed by stem
cell transplant works in treating young patients with progressive or relapsed anaplastic
large cell lymphoma.
- Improve the probability of event-free survival in children and adolescents with early
progression of anaplastic large cell lymphoma (ALCL) and/or relapse of ALCL with
CD3-positive immunophenotype treated with reinduction combination chemotherapy followed
by allogeneic or autologous stem cell transplantation.
- Determine whether a conditioning regimen comprising carmustine, etoposide phosphate,
cytarabine, and melphalan (BEAM) (without total body irradiation) for autologous stem
cell transplantation is an effective treatment for patients with relapsed CD3-negative
ALCL occurring after the intensive phase of treatment.
- Determine the impact of vinblastine in patients with late relapse of CD3-negative ALCL
- Determine overall survival and treatment-related mortality in patients treated with
- Determine acute and long-term toxicity in patients treated with these regimens.
- Determine the rate of acute and chronic graft-vs-host disease in patients treated with
OUTLINE: This is a multicenter, prospective, nonrandomized study. Patients are stratified
according to time from initial diagnosis to progression/relapse, immunophenotype of lymphoma
cells (CD3-positive + vs CD3-negative), stem cell donor availability (matched sibling donor
vs 9/10 or 10/10 matched unrelated donor), and vinblastine during frontline therapy (yes vs
no).
- Group 1 (early progression): Patients receive 1 course of ICM chemotherapy followed by
- ICM chemotherapy: Patients receive methotrexate, cytarabine, and prednisolone
intrathecally (IT) on day 1, mitoxantrone hydrochloride IV over 5 hours on days 1
and 2, carboplatin IV continuously on days 2-5 and ifosfamide IV continuously on
days 2-6.
- ICI chemotherapy: Patients receive methotrexate, cytarabine, and prednisolone
intrathecally on day 1, idarubicin IV over 4 hours on days 1 and 2, carboplatin IV
continuously on days 2-5, and ifosfamide IV continuously on days 2-6.
- Group 2 (relapsed disease and CD3-positive lymphoma cells): Patients are stratified
- Available donor: Patients receive 2 courses of CC chemotherapy and then proceed to
- Unavailable donor : Patients receive 2 courses of CC chemotherapy comprising
dexamethasone orally or IV on days 1-5, vindesine IV on day 1, cytarabine IV over
3 hours on days 1 and 2, etoposide phosphate IV over 2 hours on days 3-5, and
methotrexate, cytarabine, and prednisolone IT on day 5. Patients then receive 1
course of CVA chemotherapy comprising oral lomustine on day 1, vinblastine IV on
days 1, 8, 15, and 22, and cytarabine IV over 1 hour on days 1-5. Patients undergo
leukapheresis for collection of autologous peripheral blood stem cells after the
first and/or second course of CC chemotherapy. Patients then proceed to autologous
stem cell transplantation.
- Group 3 (relapsed disease, CD3-negative immunophenotype, and received vinblastine
during frontline therapy): Patients receive 2 courses of CC chemotherapy and 1 course
of CVA chemotherapy as described above. Patients undergo leukapheresis for collection
of autologous peripheral blood stem cells (PBSC) after the first and/or second course
of CC chemotherapy. Patients then proceed to autologous stem cell transplantation.
- Group 4 (late relapse, CD3-negative immunophenotype, and did not receive vinblastine
during frontline therapy): Patients receive vinblastine IV once weekly for 24 months.
Patients with disease progression during or relapsed disease after vinblastine therapy
undergo treatment as in group 3.
- Autologous stem cell transplantation (SCT): Patients receive a conditioning regimen
comprising carmustine IV over 1 hour on day - 7, etoposide phosphate IV over 1 hour and
cytarabine IV over 30 minutes on days - 6 to -3, and melphalan IV over 15 minutes on day
- 2. Patients undergo autologous SCT on day 0.
- Allogeneic SCT: Beginning 4-6 weeks after the start of the last chemotherapy course,
patients receive 1 of the following conditioning regimens based on age:
- Patients > 2 years of age undergo total body irradiation on days -7 to -5 and
receive thiotepa IV over 1 hour on day - 4 and etoposide IV over 4 hours on day -3.
- Patients ≤ 2 years of age receive oral busulfan 4 times daily on days -8 to -5,
thiotepa IV over 1 hour twice on day - 4, and etoposide phosphate IV over 4 hours
on day - 3. Patients undergo allogeneic SCT on day 0.
Patients undergoing SCT from an unrelated donor also receive antithymocyte globulin IV over
4 hours on days - 3 to -1.
All patients receive graft-versus-host (GVHD) prophylaxis as described below.
- GVHD prophylaxis: GVHD prophylaxis is administered as per donor status.
- Matched sibling donor: Patients receive cyclosporine IV over 2 hours or orally on
day - 1 to 60 followed by a taper.
- 10/10 or 9/10 matched unrelated donor: Patients receive cyclosporine IV over 2
hours or orally on days - 1 to 100 followed by a taper, methotrexate IV on days 1,
- Mismatched donor: Patients do not receive GVHD prophylaxis, however, CD3-positive
After completion of study treatment, patients are followed periodically for 10 years.
PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study.
St. Anna Children's Hospital, Vienna A-1090, Austria; Recruiting
Georg Mann, MD, Phone: 43-1-4017-1250
U.Z. Gasthuisberg, Leuven B-3000, Belgium; Recruiting
Anne Uyttebroeck, MD, Phone: 321-634-3841
Charles University Hospital, Prague 5 CZ-150 06, Czech Republic; Recruiting
E. Kabickova, Phone: 420-22-443-6424
University Hospital Brno, Brno CZ-662 63, Czech Republic; Recruiting
J. Sterba, Phone: 420-54-512-2614
Centre Leon Berard, Lyon 69373, France; Recruiting
Christophe Bergeron, Phone: 33-04-78-782642
Carl - Thiem - Klinkum Cottbus, Cottbus D-03048, Germany; Recruiting
D Mobius, MD, Phone: 49-355-462336
Charite University Hospital - Campus Virchow Klinikum, Berlin D-13353, Germany; Recruiting
Gunter Henze, Phone: 49-30-450-660-31
Children's Hospital, Cologne D-50924, Germany; Recruiting
Frank Berthold, MD, Phone: 49-221-478-4380, Email: frank.berthold@uk-koeln.de
Cnopf'sche Kinderklinik, Nuremberg 90419, Germany; Recruiting
A. Jobke, Phone: 49-911-3340-02
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm, Ulm D-89075, Germany; Recruiting
Klaus M. Debatin, MD, Phone: 49-731-5002-7790, Email: klaus-michael.debatin@medizin.uni-ulm.de
Dr. Horst-Schmidt-Kliniken, Wiesbaden D-65199, Germany; Recruiting
Michael Albani, MD, Phone: 49-611-432-555 ext. 667, Email: michael.albani@hsk-wiesbaden.de
Dr. von Haunersches Kinderspital der Universitaet Muenchen, Munich D-80337, Germany; Recruiting
Arndt Borkhardt, Phone: 49-89-5160-4498
Evangelisches Krankenhauus Bielfeld, Biefeld 33617, Germany; Recruiting
N. Jorch, MD, Phone: 49-52-177-278-050
Gemeinschaftskrankenhaus, Herdecke 58313, Germany; Recruiting
Christoph Tautz, MD, Phone: 49-2330-62-3914, Email: ctautz@yahoo.de
Helios Kliniken Wuppertal University Hospital, Wuppertal D-42283, Germany; Recruiting
S. Wirth, MD, Phone: 49-202-896-2444 ext. 2491, Email: swirth@wuppertal.helios-kliniken.de
Helios Klinikum Berlin, Berlin 13125, Germany; Recruiting
A. Liebeskind, Phone: 49-30-9401-2359
Helios Klinikum Erfurt, Erfurt 99089, Germany; Recruiting
Axel Sauerbrey, MD, Phone: 49-361-781-3729, Email: asauerbrey@erfurt.helios-kliniken.de
Johannes Gutenberg University, Mainz D-55101, Germany; Recruiting
P. Gutjahr, MD, Phone: 49-6131-17-2112
Johanniter-Kinderklinik, St. Augustin 53757, Germany; Recruiting
Roswitha Dickerhoff, MD, Phone: 49-22-41-2491, Email: roswitha.dickerhoft@uni-bonn.de
Kinderklinik - Universitaetsklinikum Aachen, Aachen D-52074, Germany; Recruiting
R. Mertens, MD, PhD, Phone: 49-241-808-9902, Email: rmertens@ukaachen.de
Kinderklinik - Universitaetsklinikum Rostock, Rostock D-18057, Germany; Recruiting
G. Eggers, MD, Phone: 49-381-4940
Kinderklinik der Universitaet Bonn, Bonn D-53113, Germany; Recruiting
Udo Bode, MD, Phone: 49-228-2873-3215, Email: udo.bode@ukb.uni-bonn.de
Kinderklinik Kohlhof, Neunkirchen D-66539, Germany; Recruiting
Contact Person, Phone: Not Available
Kinderklinik, Giessen D-35385, Germany; Recruiting
Alfred Reiter, MD, Phone: 49-641-994-3420
Kinderklink Siegen Deutsches Rotes Kreuz, Siegen D-57072, Germany; Recruiting
Rainer Burghard, MD, Phone: 49-271-2345-0, Email: rainer.burghard@drk-kinderklinik.de
Klinik St. Hedwig-Kinderklinik, Regensburg 93049, Germany; Recruiting
Ove Peters, Phone: 49-941-369-5404
Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster, Muenster D-48149, Germany; Recruiting
Heribert F. Juergens, MD, Phone: 49-251-834-7742, Email: jurgh@uni-muenster.de
Klinik und Poliklinik Fuer Kinder-und Jugendmedizin - Universitaetsklinikum Greifswald, Greifswald 17475, Germany; Recruiting
F. Beck, Phone: 49-3834-86-6324 ext. 6325
Kliniken der Stadt Koeln gGmbH - Kinderkrankenhaus Riehl, Cologne D-50735, Germany; Recruiting
Contact Person, Phone: 49-221-8907-5243
Klinikum Augsburg, Augsburg D-86156, Germany; Recruiting
P. Heidemann, MD, Phone: 49-821-400-3401, Email: lkk@klinikum-augsburg.de
Klinikum Bremen-Mitte, Bremen D-28205, Germany; Recruiting
Arnulf Pekrun, MD, PhD, Phone: 49-421-497-3656, Email: arnulf.pekrun@klinikum-bremen-mitte.de
Klinikum Chemnitz gGmbH, Chemnitz D-09116, Germany; Recruiting
K. Hofmann, MD, Phone: 49-371-333-241-24
Klinikum der J.W. Goethe Universitaet, Frankfurt D-60590, Germany; Recruiting
Thomas Klingebiel, MD, Phone: 49-69-6301-5094, Email: thomas.klingebiel@kgu.de
Klinikum Dortmund, Dortmund D-44137, Germany; Recruiting
Heidi Olscheswski, MD, Phone: 49-231-9532-1721
Klinikum Kassel, Kassel D-34125, Germany; Recruiting
F. K. Tegtmeyer, MD, Phone: 49-561-980-3365
Klinikum Kemperhof Koblenz, Koblenz D-56065, Germany; Recruiting
M. Rister, MD, Phone: 49-261-499-2602
Klinikum Krefeld GmbH, Krefeld D-47805, Germany; Recruiting
Schulte-Wissermann, Phone: 49-2151-32-2375
Klinikum Minden, Minden D-32423, Germany; Recruiting
W Tilmann, MD, Phone: 49-571-801-4601
Klinikum Oldenburg, Oldenburg 26133, Germany; Recruiting
Hermann Mueller, MD, Phone: 49-441-403-2013, Email: mueller.hermann@klinikum-oldenburg.de
Klinikum Schwerin, Schwerin D-19049, Germany; Recruiting
Clemens, Phone: 49-385-520-2710
Krankenanstalt Mutterhaus der Borromaerinnen, Trier D-54290, Germany; Recruiting
Wolfgang Rauh, MD, Phone: 49-651-947-2654
Krankenhaus Muenchen Schwabing, Munich 80804, Germany; Recruiting
Stefan Burdach, MD, PhD, Phone: 49-89-3068-2352
Medizinische Hochschule Hannover, Hannover D-30625, Germany; Recruiting
Karl Welte, MD, Phone: 49-511-532-6710, Email: welte.karl.h@mh-hannover.de
Olgahospital, Stuttgart D-70176, Germany; Recruiting
Stefan Bielack, MD, Phone: 49-711-99-24-61, Email: st.bielack@olgahospital.de
Saarbrucker Winterbergkliniken, Saarbrucken 66119, Germany; Recruiting
R Geib-Konig, MD, Phone: 49-681-963-2575
St. Annastift Krankenhaus, Ludwigshafen 67065, Germany; Recruiting
Barbara Selle, MD, Phone: 49-621-5702-4449
Staedtisches Klinik - Kinderklinik, Mannheim D-68167, Germany; Recruiting
M. Duerken, Phone: 49-621-383-2243
Staedtisches Klinikum - Howedestrase, Braunschweig 38118, Germany; Recruiting
Contact Person, Phone: 49-531-595-1222
Staedtisches Klinikum Karlsruhe gGmbH, Karlsruhe 76133, Germany; Recruiting
A. Leipold, Phone: 49-721-974-3311
Universitaets - Kinderklinik - Luebeck, Luebeck D-23538, Germany; Recruiting
Peter P. Bucsky, MD, Phone: 49-451-500-2956, Email: bucsky@paedia.ukl.mu-luebeck.de
Universitaets - Kinderklinik Wuerzburg, Wuerzburg D-97080, Germany; Recruiting
P. G. Schlegel, MD, Phone: 49-931-201-27-831, Email: schlegel@mail.uni-wuerzburg.de
Universitaets - Kinderklinik, Jena D-07745, Germany; Recruiting
Felix Zintl, MD, Phone: 49-3641-938-270
Universitaets - Kinderklinik, Erlangen D-91054, Germany; Recruiting
J.D. Beck, MD, Phone: 49-9131-853-3785, Email: joern.beck@kinder.imed.uni-erlangen.de
Universitaets - Kinderklinik, Leipzig D-04317, Germany; Recruiting
Dieter Koerholz, MD, Phone: 49-341-9726-246, Email: koerd@medizin.uni-leipzig.de
Universitaets - Kinderklinik, Marburg 35033, Germany; Recruiting
H. Christiansen, MD, Phone: 49-6421-286-2650
Universitaetskinderklinik - Universitaetsklinikum Freiburg, Freiburg D-79106, Germany; Recruiting
Charlotte Niemeyer, MD, Phone: 49-761-270-4506, Email: charlotte.niemeyer@uniklinik-freiburg.de
Universitaets-Kinderklinik Heidelberg, Heidelberg D-69120, Germany; Recruiting
Andreas E. Kulozik, MD, PhD, Phone: 49-6221-564-555, Email: andreas.kulozik@med.uni-heidelberg.de
Universitaetsklinikum des Saarlandes, Homburg 66421, Germany; Recruiting
Norbert Graf, Phone: 49-6841-162-4000
Universitaetsklinikum Duesseldorf, Duesseldorf D-40225, Germany; Recruiting
Contact Person, Phone: 49-211-311-7990
Universitaetsklinikum Essen, Essen D-45147, Germany; Recruiting
Bernhard Kremens, MD, Phone: 49-201-723-2453
Universitaetsklinikum Goettingen, Goettingen D-37075, Germany; Recruiting
Lothar Schweigerer, MD, Phone: 49-551-398-600
Universitaetsklinikum Tuebingen, Tuebingen D-72076, Germany; Recruiting
D. Niethammer, MD, Phone: 49-7071-298-4744
Universitatsklinikum Carl Gustav Carus, Dresden D-01307, Germany; Recruiting
M. Suttorp, MD, Phone: 49-351-458-0, Email: meinolf.suttorp@uniklinikum-dresden.de
Universitatsklinikum der MA, Magdeburg 39120, Germany; Recruiting
Uwe Mittler, MD, Phone: 49-391-67-17210
University Hospital Schleswig-Holstein - Kiel Campus, Kiel D-24105, Germany; Recruiting
Martin Schrappe, MD, PhD, Phone: 49-431-597-1620
University Medical Center Hamburg - Eppendorf, Hamburg D-20246, Germany; Recruiting
Gritta Janka-Schaub, Phone: 49-404-2803-2580
Vestische Kinderklinik, Datteln 45704, Germany; Recruiting
W. Andler, MD, Phone: 49-023-63-9750, Email: w.andler@kinderklinik-datteln.de
Our Lady's Hospital for Sick Children Crumlin, Dublin 12, Ireland; Recruiting
Fin Breatnach, MD, FRCPE, Phone: 353-1-409-6659, Email: fin.breatnach@olhsc.ie
Azienda Ospedaliera di Padova, Padova 35128, Italy; Recruiting
Angelo Rosolen, MD, Phone: 39-049-821-3579
Erasmus MC - Sophia Children's Hospital, Rotterdam 3015 GJ, Netherlands; Recruiting
Auke Beishuizen, MD, PhD, Phone: 31-10-463-6691
Akademia Medyczna im. Piastow Slaskich, Wroclaw 50-367, Poland; Recruiting
Grazyna Wrobel, Phone: 48-71-328-2040
Goeteborg University, Goeteborg S-141685, Sweden; Recruiting
Marky Ildiko, Phone: 46-31-343-4663
Kantonspital Aarau, Aarau CH-5001, Switzerland; Recruiting
R. Angst, Phone: 41-62-838-4906
Kinderspital Luzern, Lucerne
16 CH-6000, Switzerland; Recruiting
U. Caflisch, MD, Phone: 41-41-205-11-11
Ospedale "la Carita", Locarno, Locarno 6600, Switzerland; Recruiting
Luisa Nobile Buetti, MD, Phone: 41-91-756-7552
Ostschweizer Kinderspital, St. Gallen CH-9006, Switzerland; Recruiting
Jeanette Greiner, MD, Phone: 41-71-243-13-60, Email: jeanette.greiner@kispisg.ch
Universitaets-Kinderspital beider Basel, Basel CH-4005, Switzerland; Recruiting
Paul A. Imbach, MD, Phone: 41-61-685-6226
University Children's Hospital, Zurich CH-8032, Switzerland; Recruiting
Felix Niggli, MD, Phone: 41-44-266-7823
Addenbrooke's Hospital, Cambridge, England CB2 2QQ, United Kingdom; Recruiting
Amos Burke, MD, Phone: 44-1223-348-151
Birmingham Children's Hospital, Birmingham, England B4 6NH, United Kingdom; Recruiting
Martin W. English, MD, Phone: 44-121-333-8412, Email: martin.english@bch.nhs.uk
Children's Hospital - Sheffield, Sheffield, England S10 2TH, United Kingdom; Recruiting
Mary P. Gerrard, MBChB, FRCP, FRCPCH, Phone: 44-114-271-7366, Email: mary.gerrard@sch.nhs.uk
Great Ormond Street Hospital for Children, London, England WC1N 3JH, United Kingdom; Recruiting
Gill Levitt, MD, Phone: 44-20-7405-9200 ext. 0073
Institute of Child Health at University of Bristol, Bristol, England BS2 8AE, United Kingdom; Recruiting
Pamela Kearns, MD, Phone: 44-117-342-0205
Leeds Cancer Centre at St. James's University Hospital, Leeds, England LS9 7TF, United Kingdom; Recruiting
Adam Glaser, MD, Phone: 44-113-206-4984, Email: adam.glaser@leedsth.nhs.uk
Leicester Royal Infirmary, Leicester, England LE1 5WW, United Kingdom; Recruiting
Mabrouk Madi, MD, Phone: 44-116-258-5959
Middlesex Hospital, London, England W1T 3AA, United Kingdom; Recruiting
Ananth Shankar, MD, Phone: 44-20-7380-9300 ext. 9950
Oxford Radcliffe Hospital, Oxford, England 0X3 9DU, United Kingdom; Recruiting
Kate Wheeler, MD, Phone: 44-186-522-1066
Queen's Medical Centre, Nottingham, England NG7 2UH, United Kingdom; Recruiting
Martin Hewitt, MD, BSc, FRCP, FRCPCH, Phone: 44-115-924-9924 ext. 63394, Email: martin.hewitt@nuh.nhs.uk
Royal Liverpool Children's Hospital, Alder Hey, Liverpool, England L12 2AP, United Kingdom; Recruiting
Heather P. McDowell, MD, Phone: 44-151-293-3679
Royal Manchester Children's Hospital, Manchester, England M27 4HA, United Kingdom; Recruiting
Robert F. Wynn, MD, Phone: 44-161-922-2172, Email: robert.wynn@cmmc.nhs.uk
Royal Marsden - Surrey, Sutton, England SM2 5PT, United Kingdom; Recruiting
Mary Taj, MD, Phone: 44-20-8642-6011 ext. 3089
Sir James Spence Institute of Child Health at Royal Victoria Infirmary, Newcastle-Upon-Tyne, England NE1 4LP, United Kingdom; Recruiting
Juliet Hale, MD, Phone: 44-191-282-4101, Email: j.p.hale@ncl.ac.uk
Southampton General Hospital, Southampton, England SO16 6YD, United Kingdom; Recruiting
Janice A. Kohler, MD, FRCP, Phone: 44-23-8079-6942
Royal Belfast Hospital for Sick Children, Belfast, Northern Ireland BT12 6BE, United Kingdom; Recruiting
Anthony McCarthy, MD, Phone: 44-289-063-3631, Email: anthonymcarthy@royalhospital.n.i.nhs.uk
Royal Aberdeen Children's Hospital, Aberdeen, Scotland AB25 2ZG, United Kingdom; Recruiting
Veronica Neefjes, Phone: 44-1224-550-217
Royal Hospital for Sick Children, Glasgow, Scotland G3 8SJ, United Kingdom; Recruiting
Milind D. Ronghe, MD, Phone: 44-141-201-9309
Royal Hospital for Sick Children, Edinburgh, Scotland EH9 1LF, United Kingdom; Recruiting
W. Hamish Wallace, MD, Phone: 44-131-536-0426
Childrens Hospital for Wales, Cardiff, Wales CF14 4XW, United Kingdom; Recruiting
Heidi Traunecker, MD, PhD, Phone: 44-29-2074-2285, Email: heidi.traunecker@cardiffandvale.wales.nhs.uk
