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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00317408
• Other study ID #: CDR0000466639
• Secondary ID: EICNHL-ALCL-RELA
• Status: Active, not recruiting
• Phase: N/A
• First received: April 19, 2006
• Last updated: September 24, 2015
• Start date: April 2004

Study information

• Verified date: September 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 96
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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 Design

Allocation: Non-Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• anti-thymocyte globulin

Drug:
• busulfan

• carboplatin

• carmustine

• cyclosporine

• cytarabine

• dexamethasone

• etoposide phosphate

• idarubicin

• ifosfamide

• leucovorin calcium

• lomustine

• melphalan

• methotrexate

• mitoxantrone hydrochloride

• prednisolone

• thiotepa

• vinblastine sulfate

• vindesine

Procedure:
• allogeneic hematopoietic stem cell transplantation

• autologous hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Radiation:
• total-body irradiation

Locations

Country	Name	City	State
Austria	St. Anna Children's Hospital	Vienna
Belgium	U.Z. Gasthuisberg	Leuven
Czech Republic	University Hospital Brno	Brno
Czech Republic	Charles University Hospital	Prague 5
France	Centre Leon Berard	Lyon
Germany	Kinderklinik - Universitaetsklinikum Aachen	Aachen
Germany	Klinikum Augsburg	Augsburg
Germany	Charite University Hospital - Campus Virchow Klinikum	Berlin
Germany	Helios Klinikum Berlin	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	Children's Hospital	Cologne
Germany	Kliniken der Stadt Koeln gGmbH - Kinderkrankenhaus Riehl	Cologne
Germany	Carl - Thiem - Klinkum Cottbus	Cottbus
Germany	Vestische Kinderklinik	Datteln
Germany	Klinikum Dortmund	Dortmund
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
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
Germany	Kinderklinik	Giessen
Germany	Universitaetsklinikum Goettingen	Goettingen
Germany	Klinik und Poliklinik Fuer Kinder-und Jugendmedizin - Universitaetsklinikum Greifswald	Greifswald
Germany	University Medical Center Hamburg - Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
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	Luebeck
Germany	Universitatsklinikum der MA	Magdeburg
Germany	Johannes Gutenberg University	Mainz
Germany	Staedtisches Klinik - Kinderklinik	Mannheim
Germany	Universitaets - Kinderklinik	Marburg
Germany	Klinikum Minden	Minden
Germany	Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster	Muenster
Germany	Dr. von Haunersches Kinderspital der Universitaet Muenchen	Munich
Germany	Krankenhaus Muenchen Schwabing	Munich
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	Saarbrucken
Germany	Klinikum Schwerin	Schwerin
Germany	Kinderklink Siegen Deutsches Rotes Kreuz	Siegen
Germany	Johanniter-Kinderklinik	St. Augustin
Germany	Olgahospital	Stuttgart
Germany	Krankenanstalt Mutterhaus der Borromaerinnen	Trier
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Ulm
Germany	Dr. Horst-Schmidt-Kliniken	Wiesbaden
Germany	Universitaets - Kinderklinik Wuerzburg	Wuerzburg
Germany	Helios Kliniken Wuppertal University Hospital	Wuppertal
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
Italy	Azienda Ospedaliera di Padova	Padova
Netherlands	Erasmus MC - Sophia Children's Hospital	Rotterdam
Poland	Akademia Medyczna im. Piastow Slaskich	Wroclaw
Sweden	Goeteborg University	Goeteborg
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Universitaets-Kinderspital beider Basel	Basel
Switzerland	Ospedale "la Carita", Locarno	Locarno
Switzerland	Kinderspital Luzern	Lucerne 16
Switzerland	Ostschweizer Kinderspital	St. Gallen
Switzerland	University Children's Hospital	Zurich
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	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	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
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	Great Ormond Street Hospital for Children	London	England
United Kingdom	Middlesex Hospital	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

Sponsors (1)

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

Countries where clinical trial is conducted

Austria,  Belgium,  Czech Republic,  France,  Germany,  Ireland,  Italy,  Netherlands,  Poland,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival as measured by the Kaplan-Meier method			No
Secondary	Proportion of patients who are treated on protocol among all patients who meet the inclusion criteria			No
Secondary	Overall survival			No
Secondary	Acute and long term toxicity			Yes
Secondary	Rate of acute and chronic graft-vs-host disease in patients with allogeneic stem cell transplantation			No
Secondary	Treatment related mortality			No