Clinical trial NCT00343369: Combination Chemotherapy in Treating Young Patients With Acute Lymphoblastic Leukemia
Official title: Multicentric Study for the Treatment of Children With Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Leukemia
Keywords: B-cell childhood acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
T-cell childhood acute lymphoblastic leukemia
untreated childhood acute lymphoblastic leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-06-23
Enrollment: 550
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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. 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: 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.

Eligibility 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

Primary outcomes:
measure: Dose of daunorubicin hydrochloride that is equivalent to 30 mg/m² of doxorubicin hydrochloride
measure: Reduce therapy in low-risk patients without loss of efficacy
measure: Reduce neurological complications
measure: Reduce allergic reactions against asparaginase
Secondary outcomes:
Other outcomes:
Locations:
city: Biefeld
country: Germany
facility: Evangelisches Krankenhauus Bielfeld
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Greiswald
country: Germany
facility: Universitats - Kinderklinik
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Heide
country: Germany
facility: Kreskrankenhaus Kinderabteilung
city: Idar-Oberstein
country: Germany
facility: Clinic for Bone Marrow Transplantation and Hematology and Oncology
city: Krefeld
country: Germany
facility: Klinikum Krefeld GmbH
city: Leipzig
country: Germany
facility: Universitaets - Kinderklinik
city: Mainz
country: Germany
facility: Johannes Gutenberg University
city: Moenchengladbach
country: Germany
facility: Krankenhaus Neuwerk Klinik fuer Kinder und Jugendmedizin
city: Munich
country: Germany
facility: Dr. von Haunersches Kinderspital der Universitaet Muenchen
city: Munich
country: Germany
facility: Staedtisches Krankenhaus Muenchen - Harlaching
city: Regensburg
country: Germany
facility: Klinik St. Hedwig-Kinderklinik
city: Wiesbaden
country: Germany
facility: Dr. Horst-Schmidt-Kliniken
city: Wuppertal
country: Germany
facility: Helios Kliniken Wuppertal University Hospital
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Gritta Janka-Schaub
role: STUDY_CHAIR
References: