Combination Chemotherapy in Treating Young Patients With Acute Lymphoblastic Leukemia

NCT ID: NCT00343369

Last Updated: 2013-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

550 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-01-31

Brief Summary

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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. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to compare how well they work in treating young patients with acute lymphoblastic leukemia.

Detailed Description

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OBJECTIVES:

* Determine the dose of daunorubicin hydrochloride that is equivalent to 30 mg/m² of doxorubicin hydrochloride in pediatric patients with acute lymphoblastic leukemia (ALL).
* Determine whether it is possible to reduce therapy in pediatric patients with low-risk ALL and a PVA (prednisolone-vincristine-asparaginase) score of 3+4 without loss of efficacy.
* Investigate the role of single nucleotide polymorphisms of infection defense gene for infectious complications during therapy in these patients.
* Reduce neurological complications by reducing doses of intrathecal methotrexate.
* Reduce allergic reactions against asparaginase (ASP) by using pegaspargase after E. coli ASP.

OUTLINE: This is a randomized, multicenter study.

* Prephase: Patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive doxorubicin hydrochloride IV once.
* Arm II: Patients receive daunorubicin hydrochloride IV once.
* Arm III: Patients receive daunorubicin hydrochloride IV once at a higher dose than in arm II.
* Induction phase: All patients receive vincristine IV 4 times weekly, daunorubicin hydrochloride IV 3 times weekly, and oral prednisolone daily for 4 weeks.
* Intensive phase: Patients are stratified according to risk (low vs high).

* Low-risk disease\*: Patients receive 4 courses of methotrexate IV and asparaginase intramuscularly (IM).
* High-risk disease\*: Patients receive 6 courses of cyclophosphamide IV, methotrexate IV, and asparaginase IM.

All patients also receive methotrexate IV, teniposide IV, cytarabine IV, high-dose cytarabine IV, and asparaginase IM after completion of the above regimen.

* CNS phase: All patients receive intrathecal (IT) methotrexate for 3 doses and oral mercaptopurine for 4 weeks. Patients with T-cell acute lymphoblastic leukemia or patients who have blasts in cerebrospinal fluid at diagnosis or whose WBC \> 200/nL at diagnosis OR whose WBC between 100-200/nL at diagnosis and blasts \> 1/nL after prephase chemotherapy undergo cranial irradiation.
* Reinduction phase: Patients are stratified according to risk (low vs high)

* Low-risk disease\*: Patients receive 2 courses of doxorubicin hydrochloride IV, vincristine IV, and oral dexamethasone; pegaspargase IM once; and 1 course of cyclophosphamide IV, cytarabine IV, and oral thioguanine.
* High-risk disease\*: Patients receive 4 courses of doxorubicin hydrochloride IV, vincristine IV, and oral dexamethasone; pegaspargase IM twice; and 2 courses of cyclophosphamide IV, cytarabine IV, and oral thioguanine.
* Maintenance phase: All patients receive oral mercaptopurine daily and methotrexate IV once weekly for up to 2 years after diagnosis.

NOTE: \*In addition to those defined in Disease Characteristics, patients who do not achieve remission after induction phase are treated as high-risk disease, patients who achieve remission after induction phase are treated as low-risk disease

PROJECTED ACCRUAL: A total of 550 patients will be accrued for this study.

Conditions

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Leukemia

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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asparaginase

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

cytarabine

Intervention Type DRUG

daunorubicin hydrochloride

Intervention Type DRUG

dexamethasone

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

mercaptopurine

Intervention Type DRUG

methotrexate

Intervention Type DRUG

pegaspargase

Intervention Type DRUG

prednisolone

Intervention Type DRUG

teniposide

Intervention Type DRUG

thioguanine

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Diagnosed with acute B-precursor or T-cell acute lymphoblastic leukemia (ALL)
* Meets 1 of the following risk criteria:

* Low-risk disease, defined by any of the following:

* WBC \< 25/nL
* B-precursor ALL

* Excluding pro-B ALL
* High-risk disease, defined by any of the following:

* WBC ≥ 25/nL
* T-cell ALL or pro-B ALL
* Chromosomal translocation 4/11

PATIENT CHARACTERISTICS:

* Not specified

PRIOR CONCURRENT THERAPY:

* More than 7 days since prior therapy with steroids, vincristine, or daunorubicin hydrochloride
* More than 7 days since prior cytotoxic therapy
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role lead

Principal Investigators

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Gritta Janka-Schaub

Role: STUDY_CHAIR

Universitätsklinikum Hamburg-Eppendorf

Locations

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Evangelisches Krankenhauus Bielfeld

Biefeld, , Germany

Site Status RECRUITING

Klinikum Bremen-Mitte

Bremen, , Germany

Site Status RECRUITING

Universitaetsklinikum Duesseldorf

Düsseldorf, , Germany

Site Status RECRUITING

Universitats - Kinderklinik

Greiswald, , Germany

Site Status RECRUITING

University Medical Center Hamburg - Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Kreskrankenhaus Kinderabteilung

Heide, , Germany

Site Status RECRUITING

Clinic for Bone Marrow Transplantation and Hematology and Oncology

Idar-Oberstein, , Germany

Site Status RECRUITING

Klinikum Krefeld GmbH

Krefeld, , Germany

Site Status RECRUITING

Universitaets - Kinderklinik

Leipzig, , Germany

Site Status RECRUITING

Johannes Gutenberg University

Mainz, , Germany

Site Status RECRUITING

Krankenhaus Neuwerk Klinik fuer Kinder und Jugendmedizin

Mönchengladbach, , Germany

Site Status RECRUITING

Dr. von Haunersches Kinderspital der Universitaet Muenchen

Munich, , Germany

Site Status RECRUITING

Staedtisches Krankenhaus Muenchen - Harlaching

Munich, , Germany

Site Status RECRUITING

Klinik St. Hedwig-Kinderklinik

Regensburg, , Germany

Site Status RECRUITING

Dr. Horst-Schmidt-Kliniken

Wiesbaden, , Germany

Site Status RECRUITING

Helios Kliniken Wuppertal University Hospital

Wuppertal, , Germany

Site Status RECRUITING

Countries

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Germany

Facility Contacts

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N. Jorch, MD

Role: primary

Arnulf Pekrun, MD, PhD

Role: primary

Contact Person

Role: primary

James F. Beck, MD

Role: primary

Gritta Janka-Schaub

Role: primary

Streitberger

Role: primary

Wenzel Nuernberger, MD, PhD

Role: primary

P. Thomas

Role: primary

Dieter Koerholz, MD

Role: primary

P. Gutjahr, MD

Role: primary

Wolfgang Mueller, MD

Role: primary

Arndt Borkhardt

Role: primary

Papucek

Role: primary

Ove Peters

Role: primary

Gerhard Beron, MD

Role: primary

B. Dohrn, MD

Role: primary

Other Identifiers

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GER-COALL-07-03

Identifier Type: -

Identifier Source: secondary_id

EU-205104

Identifier Type: -

Identifier Source: secondary_id

CDR0000455738

Identifier Type: -

Identifier Source: org_study_id