Combination Chemotherapy in Treating Young Patients With Acute Lymphoblastic Leukemia

Multicentric Study for the Treatment of Children With Acute Lymphoblastic Leukemia

Sponsors

Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf

Source National Cancer Institute (NCI)
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.

Overall Status Unknown status
Start Date 2003-01-01
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Dose of daunorubicin hydrochloride that is equivalent to 30 mg/m² of doxorubicin hydrochloride
Reduce therapy in low-risk patients without loss of efficacy
Reduce neurological complications
Reduce allergic reactions against asparaginase
Enrollment 550
Condition
Intervention

Intervention Type: Drug

Intervention Name: asparaginase

Intervention Type: Drug

Intervention Name: cyclophosphamide

Intervention Type: Drug

Intervention Name: cytarabine

Intervention Type: Drug

Intervention Name: daunorubicin hydrochloride

Intervention Type: Drug

Intervention Name: dexamethasone

Intervention Type: Drug

Intervention Name: doxorubicin hydrochloride

Intervention Type: Drug

Intervention Name: mercaptopurine

Intervention Type: Drug

Intervention Name: methotrexate

Intervention Type: Drug

Intervention Name: pegaspargase

Intervention Type: Drug

Intervention Name: prednisolone

Intervention Type: Drug

Intervention Name: teniposide

Intervention Type: Drug

Intervention Name: thioguanine

Intervention Type: Drug

Intervention Name: vincristine sulfate

Intervention Type: Radiation

Intervention Name: radiation therapy

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

Gender:

All

Minimum Age:

1 Year

Maximum Age:

18 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Gritta Janka-Schaub Study Chair Universitätsklinikum Hamburg-Eppendorf
Location
Facility: Status: Contact:
Evangelisches Krankenhauus Bielfeld | Biefeld, 33617, Germany Recruiting N. Jorch, MD 49-52-177-278-050
Klinikum Bremen-Mitte | Bremen, D-28205, Germany Recruiting Arnulf Pekrun, MD, PhD 49-421-497-3656 [email protected]
Universitaetsklinikum Duesseldorf | Duesseldorf, D-40225, Germany Recruiting Contact Person 49-211-311-7990
Universitats - Kinderklinik | Greiswald, 17487, Germany Recruiting James F. Beck, MD 49-383-486-6325 [email protected]
University Medical Center Hamburg - Eppendorf | Hamburg, D-20246, Germany Recruiting Gritta Janka-Schaub 49-404-2803-2580
Kreskrankenhaus Kinderabteilung | Heide, 25746, Germany Recruiting Streitberger 49-481-785-911
Clinic for Bone Marrow Transplantation and Hematology and Oncology | Idar-Oberstein, D-55743, Germany Recruiting Wenzel Nuernberger, MD, PhD 49-6781-66-1582 [email protected]
Klinikum Krefeld GmbH | Krefeld, D-47805, Germany Recruiting P. Thomas 49-2151-322-375
Universitaets - Kinderklinik | Leipzig, D-04317, Germany Recruiting Dieter Koerholz, MD 49-341-9726-246 [email protected]
Johannes Gutenberg University | Mainz, D-55101, Germany Recruiting P. Gutjahr, MD 49-6131-17-2112
Krankenhaus Neuwerk Klinik fuer Kinder und Jugendmedizin | Moenchengladbach, D-41066, Germany Recruiting Wolfgang Mueller, MD 49-2161-668-2481
Dr. von Haunersches Kinderspital der Universitaet Muenchen | Munich, D-80337, Germany Recruiting Arndt Borkhardt 49-89-5160-4498
Staedtisches Krankenhaus Muenchen - Harlaching | Munich, D-81545, Germany Recruiting Papucek 49-89-6210-2710
Klinik St. Hedwig-Kinderklinik | Regensburg, 93049, Germany Recruiting Ove Peters 49-941-369-5404
Dr. Horst-Schmidt-Kliniken | Wiesbaden, D-65199, Germany Recruiting Gerhard Beron, MD 49-611-43-2564
Helios Kliniken Wuppertal University Hospital | Wuppertal, D-42283, Germany Recruiting B. Dohrn, MD 49-202-896-3823 [email protected]
Location Countries

Germany

Verification Date

2006-06-01

Keywords
Has Expanded Access No
Condition Browse
Study Design Info

Allocation: Randomized

Primary Purpose: Treatment

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