Risk-Adjusted Combination Chemotherapy in Treating Young Patients With Acute Lymphoblastic Leukemia

NCT00764907 | Unknown Phase 3

• 3 other identifiers: CDR0000613220MOTOL-ALL-IC-BFM-2002EU-20871
• Study Type: interventional
• Target: 4,000
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A donor stem cell transplant may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving combination chemotherapy before the transplant helps stop the growth of cancer cells and stop the patient's immune system from rejecting the donor's stem cells. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is studying different risk-adjusted combination chemotherapy regimens in treating young patients with acute lymphoblastic leukemia.

Conditions

Leukemia

Keywords

T-cell childhood acute lymphoblastic leukemia; B-cell childhood acute lymphoblastic leukemia; untreated childhood acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (3)

• Disease-free survival

• Event-free survival

• Overall survival

Study Arms (3)

Arm I

EXPERIMENTAL

During reinduction, patients receive 1 course of protocol II.

Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: methotrexate; Drug: thioguanine; Drug: vincristine sulfate

Arm II

EXPERIMENTAL

During reinduction, patients receive 2-3 course of protocol III and interim maintenance therapy.

Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: mercaptopurine; Drug: methotrexate; Drug: thioguanine; Drug: vincristine sulfate

Arm III

EXPERIMENTAL

During reinduction, patients are receive 2 courses of protocol II and interim maintenance therapy OR 3-block consolidation regimen and 1 course of protocol II.

Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: dexamethasone; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: leucovorin calcium; Drug: mercaptopurine; Drug: methotrexate; Drug: prednisone; Drug: thioguanine; Drug: vincristine sulfate; Drug: vindesine

Interventions

asparaginase DRUG

Given IV during reinduction

Arm I; Arm II; Arm III

cyclophosphamide DRUG

Given IV during reinduction

Arm I; Arm II; Arm III

cytarabine DRUG

Given IV during reinduction

Arm I; Arm II; Arm III

daunorubicin hydrochloride DRUG

Given IV during reinduction

Arm III

dexamethasone DRUG

Given IV or orally during reinduction

Arm I; Arm II; Arm III

doxorubicin hydrochloride DRUG

Given IV during reinduction

Arm I; Arm II; Arm III

etoposide DRUG

Given IV during reinduction

Arm III

ifosfamide DRUG

Given IV during reinduction

Arm III

leucovorin calcium DRUG

Given IV during reinduction

Arm III

mercaptopurine DRUG

Given orally during reinduction

Arm II; Arm III

methotrexate DRUG

Given orally during reinduction

Arm I; Arm II; Arm III

prednisone DRUG

Given intrathecally during reinduction

Arm III

thioguanine DRUG

Given orally during reinduction

Arm I; Arm II; Arm III

vincristine sulfate DRUG

Given IV during reinduction

Arm I; Arm II; Arm III

vindesine DRUG

Given IV during reinduction

Arm III

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Cytologically proven acute lymphoblastic leukemia (ALL) * No relapse of a previously unrecognized ALL * Patients must meet one of the following risk criteria: * Standard-risk (SR) group meeting all of the following criteria: * Blasts \< 1,000/μL in peripheral blood (PB) on day 8 * Aged 1 to \< 6 years * Initial WBC \< 20,000/μL * M1 (5%) or M2 (≥ 5% to \< 25%) blasts in bone marrow on day 15 * M1 marrow on day 33 * Intermediate-risk (IR) group meeting all of the following criteria: * Aged \< 1 or ≥ 6 years and/or WBC ≥ 20,000/μL * Blasts \< 1,000/μL in PB on day 8 * M1 or M2 marrow on day 15 * M3 (≥ 25%) marrow on day 15 OR meets SR criteria but M3 marrow on day 15 and M1 marrow on day 33 * High-risk (HR) group meeting ≥ 1 of the following criteria: * Meets IR criteria and M3 marrow on day 15 (not SR and M3 on day 15) * Blasts ≥ 1,000/μL in PB on day 8 * M2 or M3 marrow on day 33 * Translocation t(9;22) \[BCR/ABL+\] (Philadelphia chromosome-positive) or t(4;11) \[MLL/AF4+\] * No secondary ALL PATIENT CHARACTERISTICS: * No Down syndrome * No other major disease that prohibits study treatment (e.g., severe congenital heart disease) * Not requiring significant therapy modification owing to study therapy-associated complications * No complications due to other interventions * No one with missing data that are needed for the differential diagnosis, or for selection of the proper therapy arm PRIOR CONCURRENT THERAPY: * No steroids or cytostatic drugs within four weeks prior to start of study therapy

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

Sponsors & Collaborators

• University Hospital, Motol: lead

Study Sites (1)

University Hospital Motol

Prague, 150 06, Czechia

RECRUITING

Related Publications (2)

• Zuna J, Moericke A, Arens M, Koehler R, Panzer-Grumayer R, Bartram CR, Fischer S, Fronkova E, Zaliova M, Schrauder A, Stanulla M, Zimmermann M, Trka J, Stary J, Attarbaschi A, Mann G, Schrappe M, Cario G. Implications of delayed bone marrow aspirations at the end of treatment induction for risk stratification and outcome in children with acute lymphoblastic leukaemia. Br J Haematol. 2016 Jun;173(5):742-8. doi: 10.1111/bjh.13989. Epub 2016 Feb 23.

  PMID: 26913693 DERIVED

• Stary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, Gonzalez A, Izraeli S, Janic D, Jazbec J, Konja J, Kaiserova E, Kowalczyk J, Kovacs G, Li CK, Magyarosy E, Popa A, Stark B, Jabali Y, Trka J, Hrusak O, Riehm H, Masera G, Schrappe M. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol. 2014 Jan 20;32(3):174-84. doi: 10.1200/JCO.2013.48.6522. Epub 2013 Dec 16.

  PMID: 24344215 DERIVED

MeSH Terms

Conditions

Leukemia

Interventions

Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Doxorubicin; Etoposide; Ifosfamide; Leucovorin; Mercaptopurine; Methotrexate; Prednisone; Thioguanine; Vincristine; Vindesine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Oxazines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Sulfhydryl Compounds; Sulfur Compounds; Purines; Aminopterin; Pregnadienediols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Jan Stary, MD

  University Hospital, Motol

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 1, 2008
• First Posted: October 2, 2008
• Study Start: November 1, 2002
• Primary Completion: October 1, 2007
• Last Updated: July 8, 2009

Record last verified: 2009-07

Locations

CZ (1)