Combination Chemotherapy in Treating Young Patients With Acute Lymphoblastic Leukemia

Leukemia Clinical Trial

Official title:

Multicentric Study for the Treatment of Children With Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00343369
• Other study ID #: CDR0000455738
• Secondary ID: GER-COALL-07-03E
• Status: Recruiting
• Phase: N/A
• First received: June 22, 2006
• Last updated: August 23, 2013
• Start date: January 2003

Study information

• Verified date: June 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 18 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• asparaginase

• cyclophosphamide

• cytarabine

• daunorubicin hydrochloride

• dexamethasone

• doxorubicin hydrochloride

• mercaptopurine

• methotrexate

• pegaspargase

• prednisolone

• teniposide

• thioguanine

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Germany	Evangelisches Krankenhauus Bielfeld	Biefeld
Germany	Klinikum Bremen-Mitte	Bremen
Germany	Universitaetsklinikum Duesseldorf	Duesseldorf
Germany	Universitats - Kinderklinik	Greiswald
Germany	University Medical Center Hamburg - Eppendorf	Hamburg
Germany	Kreskrankenhaus Kinderabteilung	Heide
Germany	Clinic for Bone Marrow Transplantation and Hematology and Oncology	Idar-Oberstein
Germany	Klinikum Krefeld GmbH	Krefeld
Germany	Universitaets - Kinderklinik	Leipzig
Germany	Johannes Gutenberg University	Mainz
Germany	Krankenhaus Neuwerk Klinik fuer Kinder und Jugendmedizin	Moenchengladbach
Germany	Dr. von Haunersches Kinderspital der Universitaet Muenchen	Munich
Germany	Staedtisches Krankenhaus Muenchen - Harlaching	Munich
Germany	Klinik St. Hedwig-Kinderklinik	Regensburg
Germany	Dr. Horst-Schmidt-Kliniken	Wiesbaden
Germany	Helios Kliniken Wuppertal University Hospital	Wuppertal

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose of daunorubicin hydrochloride that is equivalent to 30 mg/m² of doxorubicin hydrochloride			No
Primary	Reduce therapy in low-risk patients without loss of efficacy			No
Primary	Reduce neurological complications			No
Primary	Reduce allergic reactions against asparaginase			No