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

NCT ID: NCT00317408

Last Updated: 2015-09-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

busulfan

Intervention Type: DRUG

carboplatin

Intervention Type: DRUG

carmustine

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

etoposide phosphate

Intervention Type: DRUG

idarubicin

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

lomustine

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

prednisolone

Intervention Type: DRUG

thiotepa

Intervention Type: DRUG

vinblastine sulfate

Intervention Type: DRUG

vindesine

Intervention Type: DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

total-body irradiation

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Principal Investigators

Alfred Reiter, MD

Role: STUDY_CHAIR

University Hospital Erlangen

Denise Williams, MD

Role:

Cambridge University Hospitals NHS Foundation Trust

Locations

St. Anna Children's Hospital

Vienna, , Austria

U.Z. Gasthuisberg

Leuven, , Belgium

University Hospital Brno

Brno, , Czechia

Charles University Hospital

Prague, , Czechia

Centre Leon Berard

Lyon, , France

Kinderklinik - Universitaetsklinikum Aachen

Aachen, , Germany

Klinikum Augsburg

Augsburg, , Germany

Helios Klinikum Berlin

Berlin, , Germany

Charite University Hospital - Campus Virchow Klinikum

Berlin, , Germany

Evangelisches Krankenhauus Bielfeld

Biefeld, , Germany

Kinderklinik der Universitaet Bonn

Bonn, , Germany

Staedtisches Klinikum - Howedestrase

Braunschweig, , Germany

Klinikum Bremen-Mitte

Bremen, , Germany

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Kliniken der Stadt Koeln gGmbH - Kinderkrankenhaus Riehl

Cologne, , Germany

Children's Hospital

Cologne, , Germany

Carl - Thiem - Klinkum Cottbus

Cottbus, , Germany

Vestische Kinderklinik

Datteln, , Germany

Klinikum Dortmund

Dortmund, , Germany

Universitatsklinikum Carl Gustav Carus

Dresden, , Germany

Universitaetsklinikum Duesseldorf

Düsseldorf, , Germany

Helios Klinikum Erfurt

Erfurt, , Germany

Universitaets - Kinderklinik

Erlangen, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Klinikum der J.W. Goethe Universitaet

Frankfurt, , Germany

Universitaetskinderklinik - Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Kinderklinik

Giessen, , Germany

Universitaetsklinikum Goettingen

Göttingen, , Germany

Klinik und Poliklinik Fuer Kinder-und Jugendmedizin - Universitaetsklinikum Greifswald

Greifswald, , Germany

University Medical Center Hamburg - Eppendorf

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitaets-Kinderklinik Heidelberg

Heidelberg, , Germany

Gemeinschaftskrankenhaus

Herdecke, , Germany

Universitaetsklinikum des Saarlandes

Homburg, , Germany

Universitaets - Kinderklinik

Jena, , Germany

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, , Germany

Klinikum Kassel

Kassel, , Germany

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, , Germany

Klinikum Kemperhof Koblenz

Koblenz, , Germany

Klinikum Krefeld GmbH

Krefeld, , Germany

Universitaets - Kinderklinik

Leipzig, , Germany

St. Annastift Krankenhaus

Ludwigshafen, , Germany

Universitaets - Kinderklinik - Luebeck

Lübeck, , Germany

Universitatsklinikum der MA

Magdeburg, , Germany

Johannes Gutenberg University

Mainz, , Germany

Staedtisches Klinik - Kinderklinik

Mannheim, , Germany

Universitaets - Kinderklinik

Marburg, , Germany

Klinikum Minden

Minden, , Germany

Krankenhaus Muenchen Schwabing

Munich, , Germany

Dr. von Haunersches Kinderspital der Universitaet Muenchen

Munich, , Germany

Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster

Münster, , Germany

Kinderklinik Kohlhof

Neunkirchen, , Germany

Cnopf'sche Kinderklinik

Nuremberg, , Germany

Klinikum Oldenburg

Oldenburg, , Germany

Klinik St. Hedwig-Kinderklinik

Regensburg, , Germany

Kinderklinik - Universitaetsklinikum Rostock

Rostock, , Germany

Saarbrucker Winterbergkliniken

Saarbrücken, , Germany

Johanniter-Kinderklinik

Sankt Augustin, , Germany

Klinikum Schwerin

Schwerin, , Germany

Kinderklink Siegen Deutsches Rotes Kreuz

Siegen, , Germany

Olgahospital

Stuttgart, , Germany

Krankenanstalt Mutterhaus der Borromaerinnen

Trier, , Germany

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Ulm, , Germany

Dr. Horst-Schmidt-Kliniken

Wiesbaden, , Germany

Helios Kliniken Wuppertal University Hospital

Wuppertal, , Germany

Universitaets - Kinderklinik Wuerzburg

Würzburg, , Germany

Our Lady's Hospital for Sick Children Crumlin

Dublin, , Ireland

Azienda Ospedaliera di Padova

Padua, , Italy

Erasmus MC - Sophia Children's Hospital

Rotterdam, , Netherlands

Akademia Medyczna im. Piastow Slaskich

Wroclaw, , Poland

Goeteborg University

Gothenburg, , Sweden

Kantonspital Aarau

Aarau, , Switzerland

Universitaets-Kinderspital beider Basel

Basel, , Switzerland

Ospedale "la Carita", Locarno

Locarno, , Switzerland

Kinderspital Luzern

Lucerne, , Switzerland

Ostschweizer Kinderspital

Sankt Gallen, , Switzerland

University Children's Hospital

Zurich, , Switzerland

Birmingham Children's Hospital

Birmingham, England, United Kingdom

Institute of Child Health at University of Bristol

Bristol, England, United Kingdom

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Leicester Royal Infirmary

Leicester, England, United Kingdom

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, United Kingdom

Middlesex Hospital

London, England, United Kingdom

Great Ormond Street Hospital for Children

London, England, United Kingdom

Royal Manchester Children's Hospital

Manchester, England, United Kingdom

Sir James Spence Institute of Child Health at Royal Victoria Infirmary

Newcastle upon Tyne, England, United Kingdom

Queen's Medical Centre

Nottingham, England, United Kingdom

Oxford Radcliffe Hospital

Oxford, England, United Kingdom

Children's Hospital - Sheffield

Sheffield, England, United Kingdom

Southampton General Hospital

Southampton, England, United Kingdom

Royal Marsden - Surrey

Sutton, England, United Kingdom

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, United Kingdom

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, United Kingdom

Royal Hospital for Sick Children

Edinburgh, Scotland, United Kingdom

Royal Hospital for Sick Children

Glasgow, Scotland, United Kingdom

Childrens Hospital for Wales

Cardiff, Wales, United Kingdom

Countries

Austria; Belgium; Czechia; France; Germany; Ireland; Italy; Netherlands; Poland; Sweden; Switzerland; United Kingdom

References

Knorr F, Brugieres L, Pillon M, Zimmermann M, Ruf S, Attarbaschi A, Mellgren K, Burke GAA, Uyttebroeck A, Wrobel G, Beishuizen A, Aladjidi N, Reiter A, Woessmann W; European Inter-Group for Childhood Non-Hodgkin Lymphoma. Stem Cell Transplantation and Vinblastine Monotherapy for Relapsed Pediatric Anaplastic Large Cell Lymphoma: Results of the International, Prospective ALCL-Relapse Trial. J Clin Oncol. 2020 Dec 1;38(34):3999-4009. doi: 10.1200/JCO.20.00157. Epub 2020 Jul 30.

Reference Type: DERIVED

PMID: 32730187 (View on PubMed)

Other Identifiers

EICNHL-ALCL-RELAPSE

Identifier Type: -

Identifier Source: secondary_id

AIEOP-EICNHL-ALCL-RELAPSE

Identifier Type: -

Identifier Source: secondary_id

BFM-EICNHL-ALCL-RELAPSE

Identifier Type: -

Identifier Source: secondary_id

BSPHO-EICNHL-ALCL-RELAPSE

Identifier Type: -

Identifier Source: secondary_id

DCOG-EICNHL-ALCL-RELAPSE

Identifier Type: -

Identifier Source: secondary_id

NOPHO-EICNHL-ALCL-RELAPSE

Identifier Type: -

Identifier Source: secondary_id

PPLLSG-EICNHL-ALCL-RELAPSE

Identifier Type: -

Identifier Source: secondary_id

SFCE-EICNHL-ALCL-RELAPSE

Identifier Type: -

Identifier Source: secondary_id

SHOP-EICNHL-ALCL-RELAPSE

Identifier Type: -

Identifier Source: secondary_id

CCLG-NHL-2006-01

Identifier Type: -

Identifier Source: secondary_id

EU-205118

Identifier Type: -

Identifier Source: secondary_id

EU-20618

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2005-003321-57

Identifier Type: -

Identifier Source: secondary_id

CDR0000466639

Identifier Type: -

Identifier Source: org_study_id