Combination Chemotherapy Followed By Stem Cell Transplant in Treating Young Patients With Progressive or Relapsed Anaplastic Large Cell Lymphoma
- Conditions
- Lymphoma
- Registration Number
- NCT00317408
- Lead Sponsor
- European Inter-group Cooperation on Childhood and Adolescent Non Hodgkin Lymphoma
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
Primary
* 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 who have not received vinblastine during frontline therapy.
Secondary
* Determine overall survival and treatment-related mortality in patients treated with these regimens.
* 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 allogeneic stem cell transplantation.
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 1 course of ICI chemotherapy.
* 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.
Patients then proceed to allogeneic stem cell transplantation.
* Group 2 (relapsed disease and CD3-positive lymphoma cells): Patients are stratified according to stem cell donor availability (yes vs no).
* Available donor: Patients receive 2 courses of CC chemotherapy and then proceed to allogeneic stem cell transplantation.
* 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 undergo allogeneic SCT on day 0.
* 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, 3, and 6, and leucovorin calcium IV on days 2, 4, and 7.
* Mismatched donor: Patients do not receive GVHD prophylaxis, however, CD3-positive lymphocytes are extracted from donor stem cells.
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 96
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Event-free survival as measured by the Kaplan-Meier method
- Secondary Outcome Measures
Name Time Method Proportion of patients who are treated on protocol among all patients who meet the inclusion criteria Overall survival Acute and long term toxicity Rate of acute and chronic graft-vs-host disease in patients with allogeneic stem cell transplantation Treatment related mortality
Trial Locations
- Locations (94)
University Hospital Brno
🇨🇿Brno, Czech Republic
U.Z. Gasthuisberg
🇧🇪Leuven, Belgium
Krankenhaus Muenchen Schwabing
🇩🇪Munich, Germany
Kinderklink Siegen Deutsches Rotes Kreuz
🇩🇪Siegen, Germany
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Queen's Medical Centre
🇬🇧Nottingham, England, United Kingdom
Royal Liverpool Children's Hospital, Alder Hey
🇬🇧Liverpool, England, United Kingdom
Dr. von Haunersches Kinderspital der Universitaet Muenchen
🇩🇪Munich, Germany
Krankenanstalt Mutterhaus der Borromaerinnen
🇩🇪Trier, Germany
Dr. Horst-Schmidt-Kliniken
🇩🇪Wiesbaden, Germany
Our Lady's Hospital for Sick Children Crumlin
🇮🇪Dublin, Ireland
Akademia Medyczna im. Piastow Slaskich
🇵🇱Wroclaw, Poland
Royal Manchester Children's Hospital
🇬🇧Manchester, England, United Kingdom
University Medical Center Hamburg - Eppendorf
🇩🇪Hamburg, Germany
Royal Marsden - Surrey
🇬🇧Sutton, England, United Kingdom
Klinikum Augsburg
🇩🇪Augsburg, Germany
Kinderklinik der Universitaet Bonn
🇩🇪Bonn, Germany
Carl - Thiem - Klinkum Cottbus
🇩🇪Cottbus, Germany
Klinikum der J.W. Goethe Universitaet
🇩🇪Frankfurt, Germany
Universitaetskinderklinik - Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Kinderklinik
🇩🇪Giessen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Staedtisches Klinikum Karlsruhe gGmbH
🇩🇪Karlsruhe, Germany
Kinderklinik - Universitaetsklinikum Rostock
🇩🇪Rostock, Germany
Johanniter-Kinderklinik
🇩🇪St. Augustin, Germany
Kantonspital Aarau
🇨🇭Aarau, Switzerland
Kinderklinik - Universitaetsklinikum Aachen
🇩🇪Aachen, Germany
Universitaetsklinikum Goettingen
🇩🇪Goettingen, Germany
Universitatsklinikum der MA
🇩🇪Magdeburg, Germany
Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
Klinikum Schwerin
🇩🇪Schwerin, Germany
Olgahospital
🇩🇪Stuttgart, Germany
University Children's Hospital
🇨🇭Zurich, Switzerland
Middlesex Hospital
🇬🇧London, England, United Kingdom
Centre Leon Berard
🇫🇷Lyon, France
St. Anna Children's Hospital
🇦🇹Vienna, Austria
Staedtisches Klinikum - Howedestrase
🇩🇪Braunschweig, Germany
Universitatsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Universitaetsklinikum Duesseldorf
🇩🇪Duesseldorf, Germany
Helios Klinikum Erfurt
🇩🇪Erfurt, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Klinik und Poliklinik Fuer Kinder-und Jugendmedizin - Universitaetsklinikum Greifswald
🇩🇪Greifswald, Germany
Klinikum Kassel
🇩🇪Kassel, Germany
Klinikum Kemperhof Koblenz
🇩🇪Koblenz, Germany
Universitaets - Kinderklinik - Luebeck
🇩🇪Luebeck, Germany
Staedtisches Klinik - Kinderklinik
🇩🇪Mannheim, Germany
Cnopf'sche Kinderklinik
🇩🇪Nuremberg, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Universitaets - Kinderklinik Wuerzburg
🇩🇪Wuerzburg, Germany
Helios Klinikum Berlin
🇩🇪Berlin, Germany
Evangelisches Krankenhauus Bielfeld
🇩🇪Biefeld, Germany
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Germany
Children's Hospital
🇩🇪Cologne, Germany
Vestische Kinderklinik
🇩🇪Datteln, Germany
Universitaets - Kinderklinik
🇩🇪Marburg, Germany
Universitaets-Kinderklinik Heidelberg
🇩🇪Heidelberg, Germany
University Hospital Schleswig-Holstein - Kiel Campus
🇩🇪Kiel, Germany
Saarbrucker Winterbergkliniken
🇩🇪Saarbrucken, Germany
Helios Kliniken Wuppertal University Hospital
🇩🇪Wuppertal, Germany
Universitaets-Kinderspital beider Basel
🇨🇭Basel, Switzerland
Kinderspital Luzern
🇨🇭Lucerne 16, Switzerland
Leicester Royal Infirmary
🇬🇧Leicester, England, United Kingdom
Children's Hospital - Sheffield
🇬🇧Sheffield, England, United Kingdom
Erasmus MC - Sophia Children's Hospital
🇳🇱Rotterdam, Netherlands
Birmingham Children's Hospital
🇬🇧Birmingham, England, United Kingdom
Royal Aberdeen Children's Hospital
🇬🇧Aberdeen, Scotland, United Kingdom
Sir James Spence Institute of Child Health at Royal Victoria Infirmary
🇬🇧Newcastle-Upon-Tyne, England, United Kingdom
Institute of Child Health at University of Bristol
🇬🇧Bristol, England, United Kingdom
Oxford Radcliffe Hospital
🇬🇧Oxford, England, United Kingdom
Klinikum Bremen-Mitte
🇩🇪Bremen, Germany
Klinikum Dortmund
🇩🇪Dortmund, Germany
Gemeinschaftskrankenhaus
🇩🇪Herdecke, Germany
Klinikum Krefeld GmbH
🇩🇪Krefeld, Germany
Johannes Gutenberg University
🇩🇪Mainz, Germany
Kinderklinik Kohlhof
🇩🇪Neunkirchen, Germany
Klinikum Oldenburg
🇩🇪Oldenburg, Germany
Goeteborg University
🇸🇪Goeteborg, Sweden
Klinikum Minden
🇩🇪Minden, Germany
Kliniken der Stadt Koeln gGmbH - Kinderkrankenhaus Riehl
🇩🇪Cologne, Germany
Charite University Hospital - Campus Virchow Klinikum
🇩🇪Berlin, Germany
Charles University Hospital
🇨🇿Prague 5, Czech Republic
Klinik St. Hedwig-Kinderklinik
🇩🇪Regensburg, Germany
Universitaetsklinikum des Saarlandes
🇩🇪Homburg, Germany
St. Annastift Krankenhaus
🇩🇪Ludwigshafen, Germany
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Leeds Cancer Centre at St. James's University Hospital
🇬🇧Leeds, England, United Kingdom
Ospedale "la Carita", Locarno
🇨🇭Locarno, Switzerland
Ostschweizer Kinderspital
🇨🇭St. Gallen, Switzerland
Great Ormond Street Hospital for Children
🇬🇧London, England, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, England, United Kingdom
Southampton General Hospital
🇬🇧Southampton, England, United Kingdom
Royal Belfast Hospital for Sick Children
🇬🇧Belfast, Northern Ireland, United Kingdom
Royal Hospital for Sick Children
🇬🇧Glasgow, Scotland, United Kingdom
Childrens Hospital for Wales
🇬🇧Cardiff, Wales, United Kingdom