Combination Chemotherapy Followed By Stem Cell Transplant in Treating Young Patients With Progressive or Relapsed Anaplastic Large Cell Lymphoma

September 24, 2015 updated by: European Inter-group Cooperation on Childhood and Adolescent Non Hodgkin Lymphoma

Treatment Protocol for Relapsed Anaplastic Large Cell Lymphoma of Childhood and Adolescence

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

96

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, A-1090
        • St. Anna Children's Hospital
  • Belgium
      • Leuven, Belgium, B-3000
        • U.Z. Gasthuisberg
  • Czech Republic
      • Brno, Czech Republic, CZ-662 63
        • University Hospital Brno
      • Prague 5, Czech Republic, CZ-150 06
        • Charles University Hospital
  • France
      • Lyon, France, 69373
        • Centre Leon Berard
  • Germany
      • Aachen, Germany, D-52074
        • Kinderklinik - Universitaetsklinikum Aachen
      • Augsburg, Germany, D-86156
        • Klinikum Augsburg
      • Berlin, Germany, D-13353
        • Charite University Hospital - Campus Virchow Klinikum
      • Berlin, Germany, 13125
        • Helios Klinikum Berlin
      • Biefeld, Germany, 33617
        • Evangelisches Krankenhauus Bielfeld
      • Bonn, Germany, D-53113
        • Kinderklinik der Universitaet Bonn
      • Braunschweig, Germany, 38118
        • Staedtisches Klinikum - Howedestrase
      • Bremen, Germany, D-28205
        • Klinikum Bremen-Mitte
      • Chemnitz, Germany, D-09116
        • Klinikum Chemnitz Ggmbh
      • Cologne, Germany, D-50924
        • Children's Hospital
      • Cologne, Germany, D-50735
        • Kliniken der Stadt Koeln gGmbH - Kinderkrankenhaus Riehl
      • Cottbus, Germany, D-03048
        • Carl - Thiem - Klinkum Cottbus
      • Datteln, Germany, 45704
        • Vestische Kinderklinik
      • Dortmund, Germany, D-44137
        • Klinikum Dortmund
      • Dresden, Germany, D-01307
        • Universitatsklinikum Carl Gustav Carus
      • Duesseldorf, Germany, D-40225
        • Universitaetsklinikum Duesseldorf
      • Erfurt, Germany, 99089
        • Helios Klinikum Erfurt
      • Erlangen, Germany, D-91054
        • Universitaets - Kinderklinik
      • Essen, Germany, D-45147
        • Universitaetsklinikum Essen
      • Frankfurt, Germany, D-60590
        • Klinikum der J.W. Goethe Universitaet
      • Freiburg, Germany, D-79106
        • Universitaetskinderklinik - Universitaetsklinikum Freiburg
      • Giessen, Germany, D-35385
        • Kinderklinik
      • Goettingen, Germany, D-37075
        • Universitaetsklinikum Goettingen
      • Greifswald, Germany, 17475
        • Klinik und Poliklinik Fuer Kinder-und Jugendmedizin - Universitaetsklinikum Greifswald
      • Hamburg, Germany, D-20246
        • University Medical Center Hamburg - Eppendorf
      • Hannover, Germany, D-30625
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany, D-69120
        • Universitaets-Kinderklinik Heidelberg
      • Herdecke, Germany, 58313
        • Gemeinschaftskrankenhaus
      • Homburg, Germany, 66421
        • Universitaetsklinikum des Saarlandes
      • Jena, Germany, D-07745
        • Universitaets - Kinderklinik
      • Karlsruhe, Germany, 76133
        • Staedtisches Klinikum Karlsruhe gGmbH
      • Kassel, Germany, D-34125
        • Klinikum Kassel
      • Kiel, Germany, D-24105
        • University Hospital Schleswig-Holstein - Kiel Campus
      • Koblenz, Germany, D-56065
        • Klinikum Kemperhof Koblenz
      • Krefeld, Germany, D-47805
        • Klinikum Krefeld GmbH
      • Leipzig, Germany, D-04317
        • Universitaets - Kinderklinik
      • Ludwigshafen, Germany, 67065
        • St. Annastift Krankenhaus
      • Luebeck, Germany, D-23538
        • Universitaets - Kinderklinik - Luebeck
      • Magdeburg, Germany, 39120
        • Universitatsklinikum der MA
      • Mainz, Germany, D-55101
        • Johannes Gutenberg University
      • Mannheim, Germany, D-68167
        • Staedtisches Klinik - Kinderklinik
      • Marburg, Germany, 35033
        • Universitaets - Kinderklinik
      • Minden, Germany, D-32423
        • Klinikum Minden
      • Muenster, Germany, D-48149
        • Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster
      • Munich, Germany, 80804
        • Krankenhaus Muenchen Schwabing
      • Munich, Germany, D-80337
        • Dr. von Haunersches Kinderspital der Universitaet Muenchen
      • Neunkirchen, Germany, D-66539
        • Kinderklinik Kohlhof
      • Nuremberg, Germany, 90419
        • Cnopf'sche Kinderklinik
      • Oldenburg, Germany, 26133
        • Klinikum Oldenburg
      • Regensburg, Germany, 93049
        • Klinik St. Hedwig-Kinderklinik
      • Rostock, Germany, D-18057
        • Kinderklinik - Universitaetsklinikum Rostock
      • Saarbrucken, Germany, 66119
        • Saarbrucker Winterbergkliniken
      • Schwerin, Germany, D-19049
        • Klinikum Schwerin
      • Siegen, Germany, D-57072
        • Kinderklink Siegen Deutsches Rotes Kreuz
      • St. Augustin, Germany, 53757
        • Johanniter-Kinderklinik
      • Stuttgart, Germany, D-70176
        • Olgahospital
      • Trier, Germany, D-54290
        • Krankenanstalt Mutterhaus der Borromaerinnen
      • Tuebingen, Germany, D-72076
        • Universitaetsklinikum Tuebingen
      • Ulm, Germany, D-89075
        • Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
      • Wiesbaden, Germany, D-65199
        • Dr. Horst-Schmidt-Kliniken
      • Wuerzburg, Germany, D-97080
        • Universitaets - Kinderklinik Wuerzburg
      • Wuppertal, Germany, D-42283
        • Helios Kliniken Wuppertal University Hospital
  • Ireland
      • Dublin, Ireland, 12
        • Our Lady's Hospital for Sick Children Crumlin
  • Italy
      • Padova, Italy, 35128
        • Azienda Ospedaliera Di Padova
  • Netherlands
      • Rotterdam, Netherlands, 3015 GJ
        • Erasmus MC - Sophia Children's Hospital
  • Poland
      • Wroclaw, Poland, 50-367
        • Akademia Medyczna im. Piastow Slaskich
  • Sweden
      • Goeteborg, Sweden, S-141685
        • Goeteborg University
  • Switzerland
      • Aarau, Switzerland, CH-5001
        • Kantonspital Aarau
      • Basel, Switzerland, CH-4005
        • Universitaets-Kinderspital beider Basel
      • Locarno, Switzerland, 6600
        • Ospedale "la Carita", Locarno
      • Lucerne 16, Switzerland, CH-6000
        • Kinderspital Luzern
      • St. Gallen, Switzerland, CH-9006
        • Ostschweizer Kinderspital
      • Zurich, Switzerland, CH-8032
        • University Children's Hospital
  • United Kingdom
    • England
      • Birmingham, England, United Kingdom, B4 6NH
        • Birmingham Children's Hospital
      • Bristol, England, United Kingdom, BS2 8AE
        • Institute of Child Health at University of Bristol
      • Cambridge, England, United Kingdom, CB2 2QQ
        • Addenbrooke's Hospital
      • Leeds, England, United Kingdom, LS9 7TF
        • Leeds Cancer Centre at St. James's University Hospital
      • Leicester, England, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
      • Liverpool, England, United Kingdom, L12 2AP
        • Royal Liverpool Children's Hospital, Alder Hey
      • London, England, United Kingdom, W1T 3AA
        • Middlesex Hospital
      • London, England, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital for Children
      • Manchester, England, United Kingdom, M27 4HA
        • Royal Manchester Children's Hospital
      • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
        • Sir James Spence Institute of Child Health at Royal Victoria Infirmary
      • Nottingham, England, United Kingdom, NG7 2UH
        • Queen's Medical Centre
      • Oxford, England, United Kingdom, 0X3 9DU
        • Oxford Radcliffe Hospital
      • Sheffield, England, United Kingdom, S10 2TH
        • Children's Hospital - Sheffield
      • Southampton, England, United Kingdom, SO16 6YD
        • Southampton General Hospital
      • Sutton, England, United Kingdom, SM2 5PT
        • Royal Marsden - Surrey
    • Northern Ireland
      • Belfast, Northern Ireland, United Kingdom, BT12 6BE
        • Royal Belfast Hospital for Sick Children
    • Scotland
      • Aberdeen, Scotland, United Kingdom, AB25 2ZG
        • Royal Aberdeen Children's Hospital
      • Edinburgh, Scotland, United Kingdom, EH9 1LF
        • Royal Hospital for Sick Children
      • Glasgow, Scotland, United Kingdom, G3 8SJ
        • Royal Hospital for Sick Children
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 4XW
        • Childrens Hospital for Wales

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed anaplastic large cell lymphoma (ALCL)

    • Progressive disease OR first relapse
    • No second or subsequent relapse of ALCL
  • Slides available for national central pathology review

  • Availability of 1 of the following (for allogeneic stem cell transplantation only):

    • HLA-identical matched sibling donor
    • 10/10 HLA-matched nonsibling donor (related or unrelated)
    • 9/10 HLA-matched nonsibling donor (1-antigen-mismatched related or unrelated donor)

    • < 9/10 HLA-mismatched donor (related or unrelated)

      • Stem cells may be obtained from unmanipulated bone marrow or peripheral blood stem cells after filgrastim (G-CSF) stimulation

PATIENT CHARACTERISTICS:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Adequate hepatic, renal, and cardiac function
  • No HIV infection or AIDS
  • No severe immunodeficiency
  • No other prior malignancy
  • No pre-existing disease or condition prohibiting study treatment

PRIOR CONCURRENT THERAPY:

  • At least 2 months since prior chemotherapy or radiotherapy
  • No significant pretreatment for first relapse
  • No prior organ transplantation
  • No concurrent participation in another clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Event-free survival as measured by the Kaplan-Meier method

Secondary Outcome Measures

Outcome Measure
Overall survival
Proportion of patients who are treated on protocol among all patients who meet the inclusion criteria
Acute and long term toxicity
Rate of acute and chronic graft-vs-host disease in patients with allogeneic stem cell transplantation
Treatment related mortality

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Inter-group Cooperation on Childhood and Adolescent Non Hodgkin Lymphoma

Investigators

  • Study Chair: Alfred Reiter, MD, University Hospital Erlangen
  • Denise Williams, MD, Cambridge University Hospitals NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2004

Primary Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

April 19, 2006

First Submitted That Met QC Criteria

April 21, 2006

First Posted (Estimate)

April 24, 2006

Study Record Updates

Last Update Posted (Estimate)

September 25, 2015

Last Update Submitted That Met QC Criteria

September 24, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000466639
  • EICNHL-ALCL-RELAPSE
  • AIEOP-EICNHL-ALCL-RELAPSE
  • BFM-EICNHL-ALCL-RELAPSE
  • BSPHO-EICNHL-ALCL-RELAPSE
  • DCOG-EICNHL-ALCL-RELAPSE
  • NOPHO-EICNHL-ALCL-RELAPSE
  • PPLLSG-EICNHL-ALCL-RELAPSE
  • SFCE-EICNHL-ALCL-RELAPSE
  • SHOP-EICNHL-ALCL-RELAPSE
  • CCLG-NHL-2006-01
  • EU-205118
  • EU-20618
  • EUDRACT-2005-003321-57

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma

Clinical Trials on carboplatin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Singapore

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe