Clofarabine or High-Dose Cytarabine and Pegaspargase in Children With ALL

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Universitätsklinikum Hamburg-Eppendorf
Sponsor:
Information provided by (Responsible Party):
Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT01228331
First received: October 23, 2010
Last updated: May 10, 2016
Last verified: May 2016
  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: Parallel 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 660
Study Start Date: October 2010
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I intensification (cytarabine)

LR-S patients receive HD cytarabine IV 4 x 3 g over 12 hours daily on days 29-31 and pegaspargase IV over 2 hours on days 31, 52, and 80.

LR-I and precursor B-cell ALL HR-S and HR-I patients receive HD cytarabine IV 2.500 over 3 hours twice daily on days 29-31 and 106-108 and pegaspargase IV over 2 hours on days 31, 53, 67, and 108.

Followed by standard consolidation therapy regarding to stratification containing:

methotrexate, cyclophosphamide, thioguanin, mercaptopurine, etoposide phosphate, amsacrine, cytarabine, methylprednisolone, dexamethasone, vincristine sulfate; whole-brain radiation therapy only if indicated in patients with cns involvement or T-cell ALL

Drug: Amsacrine
one block amsacrine together with etoposide and methylprednisolone for very high risk patients
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: Dexamethasone
part of reinduction therapy
Drug: Etoposide phosphate
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
Active Comparator: Arm II intensification (clofarabine)

LR-S patients receive clofarabine* IV 5 x 40 mg over 2 hours every day on days 29-33 and pegaspargase IV over 2 hours on days 33, 52, and 80.

LR-I and precursor B-cell ALL HR-S and HR-I patients receive clofarabine* IV over 2 hours on days 29-33 and pegaspargase IV over 2 hours on days 33, 53, 67, and 108.

Followed by standard consolidation therapy regarding to stratification containing:

methotrexate, cyclophosphamide, thioguanin, mercaptopurine, etoposide phosphate, amsacrine, cytarabine, methylprednisolone, dexamethasone, vincristine sulfate; whole-brain radiation therapy only if indicated in patients with cns involvement or T-cell ALL

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: Daunorubicin hydrochloride
part of induction and reinduction therapy
Drug: Dexamethasone
part of reinduction therapy
Drug: Etoposide phosphate
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
Active Comparator: Arm III reinduct.(doxorubicin hydrochl.)

LR-S patients receive doxorubicin hydrochloride IV 30 mg/m2 over 24 hours on days 1 and 8.

LR-I, HR-S and HR-I Patients receive doxorubicin hydrochloride IV 30 mg/m2 over 24 hours on days 1, 8, 22, and 29.

Followed by standard reinduction and maintenance therapy containing:

cyclophophamide, cytarabine, thioguanine, mercaptopurine, methotrexate and pegaspargase, dexamethasone, vincristine sulfate

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: Dexamethasone
part of reinduction therapy
Drug: Doxorubicin hydrochloride
part of reinduction therapy
Drug: Mercaptopurine
part of different chemotherapy blocks
Drug: Methotrexate
part of different chemotherapy blocks
Drug: Pegaspargase
part of different chemotherapy blocks
Drug: Vincristine sulfate
part of intravenous chemotherapy
Active Comparator: Arm IV reinduct.(daunorubicin hydrochl.)

LR-S patients receive daunorubicin hydrochloride IV 36 mg/m2 over 24 hours on days 1 and 8.

LR-I, HR-S and HR-I Patients receive daunorubicin hydrochloride IV 36 mg/m2 over 24 hours on days 1, 8, 22, and 29.

Followed by standard reinduction and maintenance therapy containing:

cyclophophamide, cytarabine, thioguanine, mercaptopurine, methotrexate and pegaspargase, dexamethasone, vincristine sulfate

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: Mercaptopurine
part of different chemotherapy blocks
Drug: Methotrexate
part of different chemotherapy blocks
Drug: Pegaspargase
part of different chemotherapy blocks
Drug: Vincristine sulfate
part of intravenous chemotherapy

  Show Detailed Description

  Eligibility

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

Inclusion criteria:

diagnosis after the first and before the 18th birthday AND confirmed diagnosis of acute B-precursor or or T-cell leukemia AND parents or guardians/patients give consent for inclusion in the study and transmission of data AND if none of exclusion criteria is accomplished

Exclusion criteria:

BCR/ABL rearrangement positive OR prior cytostatic treatment lasting > 7 days or prior treatment with cytostatic drugs other than vincristine, daunorubicin and prednisone OR prior severe illnesses which make treatment per the protocol impossible from the outset (BUT trisomy 21 is not an exclusion criterion) OR absence of the baseline data required for assignment to a risk group in accordance with the protocol (BUT patients for whom the MRD value could not be determined for technical reasons will be treated as protocol patients) OR the disease is a secondary malignancy or relapse OR death before the start of treatment

  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      
Dr. von Haunersches Kinderspital der Universitaet Muenchen Recruiting
Munich, Germany, D-80337
Contact: Contact Person    49-89-5160-2843      
Staedtisches Krankenhaus Muenchen - Harlaching Recruiting
Munich, Germany, D-81545
Contact: Contact Person    49-89-6210-2720      
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

Responsible Party: Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT01228331     History of Changes
Other Study ID Numbers: CDR0000686545  2009-012758-18 
Study First Received: October 23, 2010
Last Updated: May 10, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Individual Participant Data  
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Prednisolone acetate
Methylprednisolone acetate
Dexamethasone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Dexamethasone 21-phosphate
Prednisolone hemisuccinate
Prednisolone phosphate
Liposomal doxorubicin
Etoposide phosphate
Clofarabine
Pegaspargase
Cyclophosphamide
Methotrexate
Doxorubicin
Etoposide
Cytarabine
Vincristine
6-Mercaptopurine

ClinicalTrials.gov processed this record on August 23, 2016