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

NCT01228331 | Completed Phase 2 DMC

• 2 other identifiers: CDR00006865452009-012758-18
• Study Type: interventional
• Target: 745
• Locations: 1 country
• Sites: 14

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 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.

Conditions

Leukemia

Keywords

childhood acute lymphoblastic leukemia; untreated childhood acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Safety and efficacy of clofarabine combined with pegaspargase (phase II)

  minimal residual disease diagnostic, toxicity form

  at day 21 after chemotherapy

Secondary Outcomes (1)

• Incidence of infectious complications after administration of daunorubicin hydrochloride vs doxorubicin hydrochloride

  at the end of reinduction therapy

Study Arms (4)

Arm I intensification (cytarabine)

ACTIVE COMPARATOR

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; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Etoposide phosphate; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Drug: Thioguanine; Drug: Vincristine sulfate; Radiation: Whole-brain radiation therapy

Arm II intensification (clofarabine)

ACTIVE COMPARATOR

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; Drug: Clofarabine; Drug: Cyclophosphamide; Drug: Daunorubicin hydrochloride; Drug: Dexamethasone; Drug: Etoposide phosphate; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Drug: Thioguanine; Drug: Vincristine sulfate; Radiation: Whole-brain radiation therapy

Arm III reinduct.(doxorubicin hydrochl.)

ACTIVE COMPARATOR

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; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin hydrochloride; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Vincristine sulfate

Arm IV reinduct.(daunorubicin hydrochl.)

ACTIVE COMPARATOR

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; Drug: Cytarabine; Drug: Daunorubicin hydrochloride; Drug: Dexamethasone; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Vincristine sulfate

Interventions

Amsacrine DRUG

one block amsacrine together with etoposide and methylprednisolone for very high risk patients

Arm I intensification (cytarabine); Arm II intensification (clofarabine)

Clofarabine DRUG

one block clofarabine with Asparaginase for MRD positive patients after induction

Arm II intensification (clofarabine)

Cyclophosphamide DRUG

together wit MTX and ASP in consolidation and together with cytarabine and 6-TG in reinduction

Arm I intensification (cytarabine); Arm II intensification (clofarabine); Arm III reinduct.(doxorubicin hydrochl.); Arm IV reinduct.(daunorubicin hydrochl.)

Cytarabine DRUG

part of different chemotherapy blocks in consolidation and reinduction

Arm I intensification (cytarabine); Arm III reinduct.(doxorubicin hydrochl.); Arm IV reinduct.(daunorubicin hydrochl.)

Daunorubicin hydrochloride DRUG

part of induction and reinduction therapy

Arm II intensification (clofarabine); Arm IV reinduct.(daunorubicin hydrochl.)

Dexamethasone DRUG

part of reinduction therapy

Arm I intensification (cytarabine); Arm II intensification (clofarabine); Arm III reinduct.(doxorubicin hydrochl.); Arm IV reinduct.(daunorubicin hydrochl.)

Doxorubicin hydrochloride DRUG

part of reinduction therapy

Arm III reinduct.(doxorubicin hydrochl.)

Etoposide phosphate DRUG

part of different chemotherapy blocks

Arm I intensification (cytarabine); Arm II intensification (clofarabine)

Mercaptopurine DRUG

part of different chemotherapy blocks

Arm III reinduct.(doxorubicin hydrochl.); Arm IV reinduct.(daunorubicin hydrochl.)

Methotrexate DRUG

part of different chemotherapy blocks

Arm I intensification (cytarabine); Arm II intensification (clofarabine); Arm III reinduct.(doxorubicin hydrochl.); Arm IV reinduct.(daunorubicin hydrochl.)

Methylprednisolone DRUG

part of different chemotherapy blocks

Arm I intensification (cytarabine); Arm II intensification (clofarabine)

Pegaspargase DRUG

part of different chemotherapy blocks

Arm I intensification (cytarabine); Arm II intensification (clofarabine); Arm III reinduct.(doxorubicin hydrochl.); Arm IV reinduct.(daunorubicin hydrochl.)

Thioguanine DRUG

part of different chemotherapy blocks

Arm I intensification (cytarabine); Arm II intensification (clofarabine)

Vincristine sulfate DRUG

part of intravenous chemotherapy

Arm I intensification (cytarabine); Arm II intensification (clofarabine); Arm III reinduct.(doxorubicin hydrochl.); Arm IV reinduct.(daunorubicin hydrochl.)

Whole-brain radiation therapy RADIATION

patients with initial cns involvement receive cranial irradiation

Arm I intensification (cytarabine); Arm II intensification (clofarabine)

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (14)

Krankenanstalten Gilead gCmbH Neurochirurgische Klinik

Bielefeld, 33617, Germany

Location

Klinikum Bremen-Mitte

Bremen, D-28205, Germany

Location

Universitaetsklinikum Duesseldorf

Düsseldorf, D-40225, Germany

Location

Klinik und Poliklinik Fuer Kinder-und Jugendmedizin - Universitaetsklinikum Greifswald

Greifswald, 17487, Germany

Location

University Medical Center Hamburg - Eppendorf

Hamburg, D-20246, Germany

Location

Clinic for Bone Marrow Transplantation and Hematology and Oncology

Idar-Oberstein, D-55743, Germany

Location

Klinikum Krefeld GmbH

Krefeld, D-47805, Germany

Location

Universitaets - Kinderklinik

Leipzig, D-04317, Germany

Location

Johannes Gutenberg University

Mainz, D-55101, Germany

Location

Dr. von Haunersches Kinderspital der Universitaet Muenchen

Munich, D-80337, Germany

Location

Staedtisches Krankenhaus Muenchen - Harlaching

Munich, D-81545, Germany

Location

Klinik St. Hedwig-Kinderklinik

Regensburg, 93049, Germany

Location

Dr. Horst-Schmidt-Kliniken

Wiesbaden, D-65199, Germany

Location

Helios Kliniken Wuppertal University Hospital

Wuppertal, D-42283, Germany

Location

Related Links

• Clinical trial summary from the information portal of the German Society of Paediatric Oncology and Haematology (GPOH)

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Amsacrine; Clofarabine; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Doxorubicin; etoposide phosphate; Mercaptopurine; Methotrexate; Methylprednisolone; pegaspargase; Thioguanine; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminoacridines; Acridines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Sulfhydryl Compounds; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Prednisolone; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Martin Horstmann, MD

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2010
• First Posted: October 26, 2010
• Study Start: October 1, 2010
• Primary Completion: December 1, 2019
• Study Completion: November 20, 2024
• Last Updated: December 11, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (14)