Comparison of Different Combination Chemotherapy Regimens in Treating Infants With Acute Lymphoblastic Leukemia

NCT00015873 | Completed Phase 3 DMC

• 5 other identifiers: CDR0000068529ICU-INTERFANT99UKCCSG-LK-1999-05EU-20063EU-20588
• Study Type: interventional
• Target: 350
• Locations: 11 countries
• Sites: 33

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is most effective for treating infants with acute lymphoblastic leukemia. PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens in treating infants who have newly diagnosed acute lymphoblastic leukemia.

Conditions

Leukemia

Keywords

untreated childhood acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Event-free survival at 3-4 years after diagnosis

  Event-free survival

  4 years after diagnosis

Study Arms (2)

A no VIMARAM

NO INTERVENTION

No VIMARAM preceding maintenance treatment

B - VIMARAM

EXPERIMENTAL

VCR i.v. 1.5 mg/m2/d - 4 days 6-MP p.o. 25 mg/m2/d - 15 days HD-MTX p.i.(24hr) 5 g/m2 - 2 days MTX + pred I.T. (age adapted) - 2 days HD-Ara-C p.i (3hr) 3 g/m2/12 hrs -8 days L-ASP p.i. (1hr) 5.000 U/m2 - 2 days

Drug: asparaginase; Drug: cytarabine; Drug: mercaptopurine; Drug: methotrexate; Drug: prednisolone; Drug: vincristine sulfate

Interventions

asparaginase DRUG

B - VIMARAM

cytarabine DRUG

B - VIMARAM

mercaptopurine DRUG

B - VIMARAM

methotrexate DRUG

B - VIMARAM

prednisolone DRUG

B - VIMARAM

vincristine sulfate DRUG

B - VIMARAM

Eligibility Criteria

• Age: Up to 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

DISEASE CHARACTERISTICS: * Diagnosis of acute lymphoblastic leukemia (ALL) * Newly diagnosed * Morphological verification by cytochemistry and immunophenotyping * CNS or testicular leukemia at diagnosis allowed * Trisomy 21 allowed PATIENT CHARACTERISTICS: Age: * 365 days or less Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Not specified Renal: * Not specified PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No prior chemotherapy for leukemia Endocrine therapy: * At least 4 weeks since prior systemic corticosteroids * Prior inhaled steroids allowed Radiotherapy: * No prior radiotherapy for leukemia Surgery: * Not specified

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Dutch Childhood Oncology Group: lead

Study Sites (33)

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

St. Anna Children's Hospital

Vienna, A-1090, Austria

Location

Hopital Universitaire Des Enfants Reine Fabiola

Brussels, 1020, Belgium

Location

University Hospital Motol

Prague, 150 06, Czechia

Location

Hopital Saint-Louis

Paris, 75475, France

Location

University Medical Center Hamburg - Eppendorf

Hamburg, D-20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, D-30625, Germany

Location

Our Lady's Hospital for Sick Children Crumlin

Dublin, 12, Ireland

Location

Nuovo Ospedale San Gerardo at University of Milano-Bicocca

Monza, 20052, Italy

Location

Ospedale San Gerardo

Monza, 20052, Italy

Location

Erasmus MC - Sophia Children's Hospital

Rotterdam, 3015 GJ, Netherlands

Location

Ostra Sjukhuset

Gothenburg, 41685, Sweden

Location

Birmingham Children's Hospital

Birmingham, England, B4 6NH, United Kingdom

Location

Institute of Child Health at University of Bristol

Bristol, England, BS2 8AE, United Kingdom

Location

Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, CB2 2QQ, United Kingdom

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

Location

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, L12 2AP, United Kingdom

Location

Royal London Hospital

London, England, E1 1BB, United Kingdom

Location

Great Ormond Street Hospital for Children NHS Trust

London, England, WC1N 3JH, United Kingdom

Location

Central Manchester and Manchester Children's University Hospitals NHS Trust

Manchester, England, M27 4HA, United Kingdom

Location

Sir James Spence Institute of Child Health

Newcastle upon Tyne, England, NE1 4LP, United Kingdom

Location

Queen's Medical Centre

Nottingham, England, NG7 2UH, United Kingdom

Location

Oxford Radcliffe Hospital

Oxford, England, 0X3 9DU, United Kingdom

Location

Children's Hospital - Sheffield

Sheffield, England, S10 2TH, United Kingdom

Location

Southampton University Hospital NHS Trust

Southampton, England, SO16 6YD, United Kingdom

Location

Royal Marsden NHS Foundation Trust - Surrey

Sutton, England, SM2 5PT, United Kingdom

Location

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, BT12 6BE, United Kingdom

Location

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, AB25 2ZG, United Kingdom

Location

Royal Hospital for Sick Children

Edinburgh, Scotland, EH9 1LF, United Kingdom

Location

Royal Hospital for Sick Children

Glasgow, Scotland, G3 8SJ, United Kingdom

Location

Childrens Hospital for Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Related Publications (7)

• Hempel G, Relling MV, de Rossi G, Stary J, De Lorenzo P, Valsecchi MG, Barisone E, Boos J, Pieters R. Pharmacokinetics of daunorubicin and daunorubicinol in infants with leukemia treated in the interfant 99 protocol. Pediatr Blood Cancer. 2010 Mar;54(3):355-60. doi: 10.1002/pbc.22266.

  PMID: 19731319 RESULT

• Mann G, Attarbaschi A, Schrappe M, De Lorenzo P, Peters C, Hann I, De Rossi G, Felice M, Lausen B, Leblanc T, Szczepanski T, Ferster A, Janka-Schaub G, Rubnitz J, Silverman LB, Stary J, Campbell M, Li CK, Suppiah R, Biondi A, Vora A, Valsecchi MG, Pieters R; Interfant-99 Study Group. Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study. Blood. 2010 Oct 14;116(15):2644-50. doi: 10.1182/blood-2010-03-273532. Epub 2010 Jun 30.

  PMID: 20592248 RESULT

• Lonnerholm G, Valsecchi MG, De Lorenzo P, Schrappe M, Hovi L, Campbell M, Mann G, Janka-Schaub G, Li CK, Stary J, Hann I, Pieters R; Interfant-99 study group. Pharmacokinetics of high-dose methotrexate in infants treated for acute lymphoblastic leukemia. Pediatr Blood Cancer. 2009 May;52(5):596-601. doi: 10.1002/pbc.21925.

  PMID: 19132729 RESULT

• van der Linden MH, Valsecchi MG, De Lorenzo P, Moricke A, Janka G, Leblanc TM, Felice M, Biondi A, Campbell M, Hann I, Rubnitz JE, Stary J, Szczepanski T, Vora A, Ferster A, Hovi L, Silverman LB, Pieters R. Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol. Blood. 2009 Oct 29;114(18):3764-8. doi: 10.1182/blood-2009-02-204214. Epub 2009 Aug 5.

  PMID: 19657114 RESULT

• Van der Velden VH, Corral L, Valsecchi MG, Jansen MW, De Lorenzo P, Cazzaniga G, Panzer-Grumayer ER, Schrappe M, Schrauder A, Meyer C, Marschalek R, Nigro LL, Metzler M, Basso G, Mann G, Den Boer ML, Biondi A, Pieters R, Van Dongen JJ; Interfant-99 Study Group. Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol. Leukemia. 2009 Jun;23(6):1073-9. doi: 10.1038/leu.2009.17. Epub 2009 Feb 12.

  PMID: 19212338 RESULT

• Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, Hovi L, LeBlanc T, Szczepanski T, Ferster A, Janka G, Rubnitz J, Silverman L, Stary J, Campbell M, Li CK, Mann G, Suppiah R, Biondi A, Vora A, Valsecchi MG. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet. 2007 Jul 21;370(9583):240-250. doi: 10.1016/S0140-6736(07)61126-X.

  PMID: 17658395 RESULT

• Pieters R, Schrappe M, de Lorenzo P, et al.: Outcome of infants less than one year of age with acute lymphoblastic leukemia treated with the Interfant-99 protocol. [Abstract] Blood 108 (11): A-145, 2006.

  RESULT

MeSH Terms

Conditions

Leukemia

Interventions

Asparaginase; Cytarabine; Mercaptopurine; Methotrexate; Prednisolone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Rob Pieters, MD, MSC, PhD

  Erasmus MC-Sophia Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2001
• First Posted: January 27, 2003
• Study Start: May 1, 1999
• Primary Completion: February 1, 2006
• Study Completion: December 1, 2009
• Last Updated: February 17, 2014

Record last verified: 2014-02

Locations

CZ (1); DE (2); FR (1); BE (1); SE (1); IE (1); AU (1); NL (1); GB (20); US (2); IT (2)