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Two Combination Chemotherapy Regimens in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Prince of Wales Hospital, Shatin, Hong Kong
Sponsor:
Collaborators:
Technology R&D Program, Ministry of Science & Technology, People Republic of China.
Children Cancer Foundation Hong Kong
Information provided by (Responsible Party):
Chi Kong Li, Prince of Wales Hospital, Shatin, Hong Kong
ClinicalTrials.gov Identifier:
NCT00707083
First received: June 27, 2008
Last updated: April 28, 2013
Last verified: April 2013

June 27, 2008
April 28, 2013
May 2008
December 2013   (final data collection date for primary outcome measure)
Bone marrow suppression and liver toxicity [ Time Frame: 24 or 30 months of chemotherapy ] [ Designated as safety issue: Yes ]
compare marrow suppression in the two arms of maintenance treatment
  • Bone marrow suppression [ Designated as safety issue: Yes ]
  • Liver toxicity [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00707083 on ClinicalTrials.gov Archive Site
  • overall and event-free survival [ Time Frame: 3 years after stop treatment ] [ Designated as safety issue: No ]
  • Hospitalization rate during maintenance treatment [ Time Frame: 24 or 30 months after chemotherapy ] [ Designated as safety issue: Yes ]
  • Infection rate [ Designated as safety issue: Yes ]
  • Hospitalization rate [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Two Combination Chemotherapy Regimens in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia
A Multicenter Study of Treatment Protocol for Childhood Acute Lymphoblastic Leukemia in China, 2008.

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 clinical trial is studying the side effects of two combination chemotherapy regimens and to see how well they work in treating children with newly diagnosed acute lymphoblastic leukemia.

OBJECTIVES:

Primary

  • Compare the incidence of marrow suppression with 2 methods of maintenance treatment in children with acute lymphoblastic leukemia.
  • Compare the incidence of liver toxicity with 2 methods of maintenance treatment in these patients.

Secondary

  • Determine any difference in infection rates and related hospitalizations in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (high vs intermediate vs standard), age in years (0 to 5 vs 6 to 9 vs 10 to 17), and sex.

  • Patients with standard-risk disease:

    • Induction therapy: Patients receive prednisolone IV or orally three times daily on days 1-7; oral dexamethasone three times daily on days 8-28; asparaginase IV over 1 hour or intramuscularly once on days 8, 11, 14, 17, 20, 23, 26, and 29; vincristine IV once on days 8, 15, 22, and 29; daunorubicin hydrochloride IV over 1 hour on days 8 and 15; and methotrexate intrathecally (IT) once on days 1, 15, and 33.
    • Early intensification (EI) therapy: Patients receive cyclophosphamide IV over 1 hour on day 36, cytarabine IV continuously on days 38-41 and 45-48, oral mercaptopurine once daily on days 36-50, and methotrexate IT on days 38 and 45.
    • Consolidation therapy: Two weeks after completing EI therapy, patients receive oral mercaptopurine once daily on days 1-56 and methotrexate IV over 24 hours and IT on days 8, 22, 36, and 50.
    • Delayed intensification (DI) therapy:

      • DI/a: Patients receive dexamethasone orally or IV three times daily on days 1-7 and 15-21, doxorubicin hydrochloride IV over 1 hour on days 1, 8, and 15; vincristine IV on days 1, 8, and 15; and asparaginase subcutaneously (SC) or IV over 1 hour on days 1, 4, 8, and 11.
      • DI/b: Patients receive cyclophosphamide IV over 1 hour on day 29, cytarabine IV continuously on days 31-34 and 38-41, oral thioguanine once daily on days 29-42, and methotrexate IT on days 31 and 38.
    • Maintenance therapy: Patients are randomized to one of two treatment arms. Patients who do not consent for randomization receive conventional therapy (arm I).

      • Arm I (conventional): Patients receive oral mercaptopurine and oral methotrexate on days 1-56, dexamethasone IV on days 1-5 and 29-33, vincristine IV on days 1 and 29, and methotrexate IT on day 50. Treatment repeats every 8 weeks for up to 8 courses for girls or 11 courses for boys.
      • Arm II (intervention): Patients receive oral mercaptopurine once daily on days 8-28 and 36-56; oral methotrexate once on days 8,15, 22, 36, 43, and 50; dexamethasone IV on days 1-5 and 29-33; and vincristine IV on days 1 and 29. Patients also receive methotrexate IT on day 1, every 8 weeks, for 8 courses.
  • Patients with intermediate-risk disease:

    • Induction therapy: Patients receive prednisolone, dexamethasone, and asparaginase as in standard-risk induction therapy. Patients also receive vincristine IV and daunorubicin hydrochloride IV over 1 hour on days 8, 15, 22, and 29; methotrexate IT on day 1; and triple intrathecal therapy (TIT; high-dose methotrexate, cytarabine, hydrocortisone sodium succinate) on days 15 and 33.
    • First EI therapy: Patients receive cyclophosphamide, cytarabine, and mercaptopurine as in standard-risk EI. Patients also receive TIT on day 38.
    • Second EI therapy: Beginning 2 weeks after completing first EI, patients receive cyclophosphamide over 1 hour on day 1, oral mercaptopurine on days 1-14, cytarabine IV on days 3-6 and 10-13, and TIT on day 3.
    • Consolidation therapy: Beginning 2 weeks after completing second EI, patients receive mercaptopurine as in standard-risk consolidation therapy. Patients also receive methotrexate IV over 24 hours and TIT on days 8, 22, 36, and 50.
    • First DI therapy: Patients receive treatment as in standard-risk DI.
    • Interim maintenance therapy: Patients receive oral mercaptopurine and oral methotrexate on days 1-56.
    • Second DI therapy: Patients receive DI/a and D1/b (without methotrexate) as in standard-risk DI. Patients also receive TIT on days 31 and 38.
    • Maintenance therapy: Patients are randomized to 1 of 2 treatment arms:

      • Arm I (conventional): Patients receive mercaptopurine, methotrexate, dexamethasone, and vincristine as in standard-risk maintenance therapy arm I. Patients also receive TIT on day 50. Treatment repeats every 8 weeks for up to 8 courses for girls or 11 courses for boys.
      • Arm II (intervention): Patients receive treatment as in standard-risk maintenance therapy arm II.
  • Patients with high-risk disease:

    • Induction therapy: Patients receive treatment as in intermediate-risk induction therapy.
    • First EI therapy: Patients receive treatment as in intermediate-risk first EI.
    • Second EI therapy: Patients receive treatment as in intermediate-risk second EI.
    • Consolidation therapy (interval between blocks is 2 weeks):

      • Block 1: Patients receive dexamethasone orally or IV three times daily on days 1-5, vincristine IV on days 1 and 6, high-dose methotrexate IV over 24 hours on day 1, cyclophosphamide IV over 1 hour twice daily on days 2-4, cytarabine IV over 3 hours twice on day 5, asparaginase IV over 2 hours on days 6 and 11, and TIT on day 1.
      • Block 2: Patients receive dexamethasone, high-dose methotrexate, asparaginase, and TIT as in block 1. Patients also receive vindesine IV twice daily on days 1 and 6, ifosfamide IV over 1 hour twice daily on days 2-4, and daunorubicin hydrochloride IV over 24 hours on day 5.
      • Block 3: Patients receive dexamethasone and asparaginase as in block 1. Patients also receive high-dose cytarabine IV over 3 hours twice daily on days 1 and 2, etoposide IV over 1 hour five times on days 3-5, and TIT on day 5.
    • Blocks 1-3 are then repeated once. Patients then proceed to delayed intensification therapy.
    • Delayed intensification therapy: Patients receive dexamethasone orally or IV three times daily on days 1-7 and 15-21; doxorubicin hydrochloride IV and vincristine IV on days 8, 15, 22, and 29; and asparaginase IV on days 8, 11, 15, and 18. Patients also receive cyclophosphamide IV on day 36, cytarabine IV on days 38-41 and 45-48, thioguanine IV on days 36-49, and TIT on days 38 and 45.
    • Maintenance therapy: Patients receive oral mercaptopurine and oral methotrexate once daily on days 1-14, cyclophosphamide over 1 hour and cytarabine over 1 hour once between days 15-21, oral dexamethasone two or three times daily for 5 days between days 29-35, vincristine IV on day 29, and TIT on day 22. Treatment repeats every 4 weeks. After 10 courses, patients no longer receive TIT. After 12 courses, patients no longer receive cyclophosphamide and cytarabine. At this time patients continue mercaptopurine and methotrexate on days 1-21. After 20 courses, patients no longer receive dexamethasone or vincristine. At this time, patients continue mercaptopurine and methotrexate on days 1-28. Females receive up to 17 courses and males up to 23 courses.

Some patients may also undergo radiotherapy or stem cell transplantation.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Drug: dexamethasone
    Given IV
  • Drug: mercaptopurine
    Given orally
  • Drug: methotrexate
    Given orally
  • Drug: vincristine sulfate
    Given IV
  • Active Comparator: Standard- or Intermediate-Risk Maintenance Arm I
    Patients receive oral mercaptopurine and oral methotrexate on days 1-56, dexamethasone IV on days 1-5 and 29-33, vincristine IV on days 1 and 29, and methotrexate IT on day 50. Treatment repeats every 8 weeks for up to 8 (girls)-11 (boys) courses.
    Interventions:
    • Drug: dexamethasone
    • Drug: mercaptopurine
    • Drug: methotrexate
    • Drug: vincristine sulfate
  • Experimental: Standard- or Intermediate-Risk Maintenance Arm II
    Patients receive oral mercaptopurine once daily on days 8-28 and 36-56; oral methotrexate once on days 8,15, 22, 36, 43, and 50; dexamethasone IV on days 1-5 and 29-33; and vincristine IV on days 1 and 29. Patients also receive methotrexate IT on day 1, every 8 weeks, for 8 courses.
    Interventions:
    • Drug: dexamethasone
    • Drug: mercaptopurine
    • Drug: methotrexate
    • Drug: vincristine sulfate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
2500
December 2016
December 2013   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Newly diagnosed acute lymphoblastic leukemia meeting 1 of the following risk definitions:

    • Standard-risk disease:

      • Age 1 to 9 years
      • WBC < 50/mm^3 OR TEL/AML1-positive disease
      • Good response to prior prednisone (day 8 peripheral blood blast < 1,000/mm^3)
      • None of the following subtypes:

        • T-cell
        • t(9;22)
        • t(4;11)
        • t(1;19)
        • Molecular
      • Bone marrow (BM) M1 or M2 on day 15, BM remission (< 5% blast) on day 33
    • Intermediate-risk disease:

      • Good response to prior prednisone
      • BM M1/M2 on day 15
      • Meets 1 of the following criteria:

        • At least 10 years old
        • WBC > 50/mm^3
        • Under 1 year old without MLL gene rearrangement
        • T-cell OR t(1;19) OR E2A/PBX1
        • Standard-risk patient with BM M3 on day 15
        • If minimal residual disease (MRD) available, day 33 MRD < 10^-2
    • High-risk disease, meeting 1 of the following criteria:

      • Poor response to prior prednisone
      • t(9;22), BCR/ABL, t(4;11), OR MLL/AF4
      • Intermediate-risk patient with BM M3 on day 15
      • BM M2/M3 on day 33
      • If MRD available, flow cytometry/PCR > 10% on days 15 OR MRD > 10^-2 on day 33 OR MRD (before mM or M phase) > 10^-3 on day 84

PATIENT CHARACTERISTICS:

  • Not specified

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
Both
up to 17 Years
No
China
 
NCT00707083
POWH-CRE-2008.077-T, CDR0000595184
No
Chi Kong Li, Prince of Wales Hospital, Shatin, Hong Kong
Prince of Wales Hospital, Shatin, Hong Kong
  • Technology R&D Program, Ministry of Science & Technology, People Republic of China.
  • Children Cancer Foundation Hong Kong
Principal Investigator: Chi-Kong Li, MD Prince of Wales Hospital
Prince of Wales Hospital, Shatin, Hong Kong
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP