Clofarabine or High-Dose Cytarabine, Pegaspargase, and Combination Chemotherapy Followed by Daunorubicin Hydrochloride or Doxorubicin Hydrochloride in Treating Young Patients With Acute Lymphoblastic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2011 by Universitätsklinikum Hamburg-Eppendorf
Sponsor:
Information provided by (Responsible Party):
Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT01228331
First received: October 23, 2010
Last updated: November 17, 2011
Last verified: November 2011
  Purpose

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 once drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high-energy x-rays to kill cancer cells. It is not yet known whether giving clofarabine or high-dose cytarabine, pegaspargase, and combination chemotherapy followed by daunorubicin hydrochloride or doxorubicin hydrochloride is more effective in treating young patients with acute lymphoblastic leukemia.

PURPOSE: This randomized phase II/III trial is studying the side effects of giving clofarabine compared with giving high-dose cytarabine, pegaspargase, and combination chemotherapy followed by daunorubicin hydrochloride or doxorubicin hydrochloride and to see how well it works in treating young patients with T-cell acute lymphoblastic leukemia or precursor B-cell acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia
Drug: amsacrine
Drug: clofarabine
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: etoposide phosphate
Drug: mercaptopurine
Drug: methotrexate
Drug: methylprednisolone
Drug: pegaspargase
Drug: thioguanine
Drug: vincristine sulfate
Radiation: whole-brain radiation therapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Multi-Center Treatment Study (COALL 08-09) to Improve the Survival of Children With Acute Lymphoblastic Leukemia on Behalf of the German Society of Pediatric Hematology and Oncology

Resource links provided by NLM:


Further study details as provided by Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:
  • Safety and efficacy of clofarabine combined with pegaspargase (phase II) [ Time Frame: at day 21 after chemotherapy ] [ Designated as safety issue: Yes ]
  • Cytotoxic efficacy of clofarabine compared with high-dose (HD) cytarabine in combination with pegaspargase (phase III) [ Time Frame: at day 21 after chemotherapy ] [ Designated as safety issue: Yes ]
  • Incidence of infectious complications after administration of daunorubicin hydrochloride vs doxorubicin hydrochloride [ Time Frame: at the end of reinduction therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety profiles of clofarabine and pegaspargase vs HD cytarabine and pegaspargase [ Time Frame: at day 21 after chemotherapy ] [ Designated as safety issue: Yes ]
  • Efficacy of clofarabine and pegaspargase and HD cytarabine and pegaspargase, in terms of minimal-residual disease (MRD) vs methotrexate, cyclophosphamide, and asparaginase in study COALL-07-03 [ Time Frame: at day 21 after chemotherapy ] [ Designated as safety issue: No ]
  • Impact of MRD-based stratification in COALL-09 on overall survival and event-free survival in a historical comparison of previous COALL studies [ Time Frame: after 5 years observation ] [ Designated as safety issue: No ]

Estimated Enrollment: 660
Study Start Date: October 2010
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: amsacrine
    one block amsacrine together with etoposide and methylprednisolone for very high risk patients
    Drug: clofarabine
    one block clofarabine with Asparaginase for MRD positive patients after induction
    Drug: cyclophosphamide
    together wit MTX and ASP in consolidation and together with cytarabine and 6-TG in reinduction
    Drug: cytarabine
    part of different chemotherapy blocks in consolidation and reinduction
    Drug: daunorubicin hydrochloride
    part of induction and reinduction therapy
    Drug: dexamethasone
    part of reinduction therapy
    Drug: doxorubicin hydrochloride
    part of reinduction therapy
    Drug: etoposide phosphate
    part of different chemotherapy blocks
    Drug: mercaptopurine
    part of different chemotherapy blocks
    Drug: methotrexate
    part of different chemotherapy blocks
    Drug: methylprednisolone
    part of different chemotherapy blocks
    Drug: pegaspargase
    part of different chemotherapy blocks
    Drug: thioguanine
    part of different chemotherapy blocks
    Drug: vincristine sulfate
    part of intravenous chemotherapy
    Radiation: whole-brain radiation therapy
    patients with initial cns involvement receive cranial irradiation
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) or T-cell ALL* after October 1st 2009

    • No B-cell ALL NOTE: *Patients with non-Hodgkin lymphoma of the T-cell or B-cell precursor type are included in the observation group.
  • Meets 1 of the following risk group criteria:

    • Low-risk (LR) disease meeting all of the following criteria:

      • WBC < 25/nL at diagnosis
      • Age ≥ 1 to < 10 years
      • Common ALL or precursor B-cell ALL
      • Complete remission on day 29 (after induction therapy)
      • No 11q23 rearrangement
      • No hypodiploid chromosome number
    • High-risk (HR) disease meeting any of the following criteria:

      • WBC ≥ 25/nL at diagnosis
      • Age ≥ 10 years
      • Progenitor B-cell ALL or T-cell ALL
      • No complete remission on day 29
      • 11q23 rearrangement
      • Hypodiploid chromosome number (< 45 chromosomes)
  • Must meet 1 of the following criteria regarding minimal-residual disease (MRD):

    • LR disease after induction (on day 29):

      • LR-reduced (LR-R): MRD negative
      • LR-standard (LR-S): MRD positive but < 10^-3 or no evaluable MRD results
      • LR-intensified (LR-I): MRD ≥ 10^-3
    • HR disease after induction and intensification ????? (on day 29 and/or day 43):

      • HR-reduced (HR-R):

        • T-cell ALL: MRD < 10^-3 on day 29
        • Precursor B-cell ALL: MRD negative on day 29
      • HR-standard (HR-S):

        • T-cell ALL: MRD ≥ 10^-3 on day 29 and < 10^-3 on day 43
        • Precursor B-cell ALL: MRD positive on day 29 but < 10^-3 or no evaluable MRD results
      • HR-intensified (HR-I):

        • T-cell ALL: MRD ≥ 10^-3 on day 43
        • Precursor B-cell ALL: MRD ≥ 10^-3 on day 29
  • Must be under treatment at 1 of the participating hospitals
  • No disease that is a secondary malignancy or relapsed
  • After induction, patients with translocation t(9;22) will receive treatment as part of the European Study on Philadelphia-positive leukemia (EsPhALL)
  • bcr-abl-positive patients will be assigned and treated according to different protocols

PATIENT CHARACTERISTICS:

  • No prior severe illness that makes treatment on this study impossible from the outset

    • Trisomy 21 (Down syndrome) allowed

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior cytostatic treatment lasting > 7 days
  • No prior treatment with drugs other than vincristine sulfate, daunorubicin hydrochloride, and prednisone
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01228331

Locations
Germany
Krankenanstalten Gilead gCmbH Neurochirurgische Klinik Recruiting
Bielefeld, Germany, 33617
Contact: Contact Person    49-521-144-2728      
Klinikum Bremen-Mitte Recruiting
Bremen, Germany, D-28205
Contact: Contact Person    49-421-497-5413      
Universitaetsklinikum Duesseldorf Recruiting
Duesseldorf, Germany, D-40225
Contact: Contact Person    49-211-81-17662      
Klinik und Poliklinik Fuer Kinder-und Jugendmedizin - Universitaetsklinikum Greifswald Recruiting
Greifswald, Germany, 17487
Contact: Contact Person    49-3834-86-6321      
University Medical Center Hamburg - Eppendorf Recruiting
Hamburg, Germany, D-20246
Contact: Contact Person    49-407-4105-2580    horstmann@uke.uni-hamburg.de   
Clinic for Bone Marrow Transplantation and Hematology and Oncology Recruiting
Idar-Oberstein, Germany, D-55743
Contact: Contact Person    49-6781-66-1582      
Klinikum Krefeld GmbH Recruiting
Krefeld, Germany, D-47805
Contact: Contact Person    49-2151-322-375      
Universitaets - Kinderklinik Recruiting
Leipzig, Germany, D-04317
Contact: Contact Person    49-341-9726-113      
Johannes Gutenberg University Recruiting
Mainz, Germany, D-55101
Contact: Contact Person    49-6131-17-2642      
Staedtisches Krankenhaus Muenchen - Harlaching Recruiting
Munich, Germany, D-81545
Contact: Contact Person    49-89-6210-2720      
Dr. von Haunersches Kinderspital der Universitaet Muenchen Recruiting
Munich, Germany, D-80337
Contact: Contact Person    49-89-5160-2843      
Klinik St. Hedwig-Kinderklinik Recruiting
Regensburg, Germany, 93049
Contact: Contact Person    49-941-2080-493      
Dr. Horst-Schmidt-Kliniken Recruiting
Wiesbaden, Germany, D-65199
Contact: Contact Person    49-611-43-2564      
Helios Kliniken Wuppertal University Hospital Recruiting
Wuppertal, Germany, D-42283
Contact: Contact Person    49-202-896-2444      
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Investigators
Principal Investigator: Martin Horstmann, MD Universitätsklinikum Hamburg-Eppendorf
  More Information

Additional Information:
No publications provided

Responsible Party: Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT01228331     History of Changes
Other Study ID Numbers: CDR0000686545, GPOH-COALL-08-09, EUDRACT-2009-012758-18, EU-21076
Study First Received: October 23, 2010
Last Updated: November 17, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
T-cell childhood acute lymphoblastic leukemia
untreated childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Cytarabine
Methotrexate
Thioguanine
Clofarabine
Cyclophosphamide
Liposomal doxorubicin
Etoposide phosphate
Pegaspargase
Amsacrine
Daunorubicin
Dexamethasone
Doxorubicin
Etoposide
Methylprednisolone Hemisuccinate
Prednisolone
Vincristine
BB 1101
Dexamethasone acetate
Methylprednisolone acetate
Prednisolone acetate

ClinicalTrials.gov processed this record on September 14, 2014