Combination Chemotherapy in Treating Young Patients With Acute Lymphoblastic Leukemia

August 23, 2013 updated by: Universitätsklinikum Hamburg-Eppendorf

Multicentric Study for the Treatment of Children With Acute Lymphoblastic Leukemia

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

550

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Biefeld, Germany, 33617
        • Recruiting
        • Evangelisches Krankenhauus Bielfeld
        • Contact:
          • N. Jorch, MD
          • Phone Number: 49-52-177-278-050
      • Bremen, Germany, D-28205
      • Duesseldorf, Germany, D-40225
        • Recruiting
        • Universitaetsklinikum Duesseldorf
        • Contact:
          • Contact Person
          • Phone Number: 49-211-311-7990
      • Greiswald, Germany, 17487
        • Recruiting
        • Universitats - Kinderklinik
        • Contact:
      • Hamburg, Germany, D-20246
        • Recruiting
        • University Medical Center Hamburg - Eppendorf
        • Contact:
          • Gritta Janka-Schaub
          • Phone Number: 49-404-2803-2580
      • Heide, Germany, 25746
        • Recruiting
        • Kreskrankenhaus Kinderabteilung
        • Contact:
          • Streitberger
          • Phone Number: 49-481-785-911
      • Idar-Oberstein, Germany, D-55743
        • Recruiting
        • Clinic for Bone Marrow Transplantation and Hematology and Oncology
        • Contact:
      • Krefeld, Germany, D-47805
        • Recruiting
        • Klinikum Krefeld GmbH
        • Contact:
          • P. Thomas
          • Phone Number: 49-2151-322-375
      • Leipzig, Germany, D-04317
      • Mainz, Germany, D-55101
        • Recruiting
        • Johannes Gutenberg University
        • Contact:
          • P. Gutjahr, MD
          • Phone Number: 49-6131-17-2112
      • Moenchengladbach, Germany, D-41066
        • Recruiting
        • Krankenhaus Neuwerk Klinik fuer Kinder und Jugendmedizin
        • Contact:
          • Wolfgang Mueller, MD
          • Phone Number: 49-2161-668-2481
      • Munich, Germany, D-80337
        • Recruiting
        • Dr. von Haunersches Kinderspital der Universitaet Muenchen
        • Contact:
          • Arndt Borkhardt
          • Phone Number: 49-89-5160-4498
      • Munich, Germany, D-81545
        • Recruiting
        • Staedtisches Krankenhaus Muenchen - Harlaching
        • Contact:
          • Papucek
          • Phone Number: 49-89-6210-2710
      • Regensburg, Germany, 93049
        • Recruiting
        • Klinik St. Hedwig-Kinderklinik
        • Contact:
          • Ove Peters
          • Phone Number: 49-941-369-5404
      • Wiesbaden, Germany, D-65199
        • Recruiting
        • Dr. Horst-Schmidt-Kliniken
        • Contact:
          • Gerhard Beron, MD
          • Phone Number: 49-611-43-2564
      • Wuppertal, Germany, D-42283

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 months to 16 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universitätsklinikum Hamburg-Eppendorf

Investigators

  • Study Chair: Gritta Janka-Schaub, Universitätsklinikum Hamburg-Eppendorf

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Study Registration Dates

First Submitted

June 22, 2006

First Submitted That Met QC Criteria

June 22, 2006

First Posted (Estimate)

June 23, 2006

Study Record Updates

Last Update Posted (Estimate)

August 26, 2013

Last Update Submitted That Met QC Criteria

August 23, 2013

Last Verified

June 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000455738
  • GER-COALL-07-03
  • EU-205104

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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