A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia

Sponsor
South China Children's Leukemia Group (Other)
Overall Status
Completed
CT.gov ID
NCT02200978
Collaborator
(none)
176
1
2
121
1.5

Study Details

Study Description

Brief Summary

Outcome of acute promyelocytic leukemia (APL) has greatly improved since the introduction of all-trans-retinoic acid (ATRA). Treatment with ATRA and anthracycline-based chemotherapy (ATRA + chemotherapy) decreases relapses of the disease as well as early hemorrhagic deaths. Nowadays patients with APL have an event-free survival (EFS) of up to 80%. However, there remains a subset of the patients in whom the disease relapses. Recently, a randomized prospective study showed that the addition of ATO to "ATRA + chemotherapy" treatment protocol had a significantly higher EFS in patients with APL than those treated with "ATRA + chemotherapy" protocol. The patients treated with "ATO + ATRA + chemotherapy" had a five years EFS of 89.2%. Moreover, a recent study showed that Indigo naturalis formula (RIF), a traditional Chinese medicine with tetraarsenic tetrasulfide (As4S4), indirubin, and tanshinone IIA as major active ingredients, yielded synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro . It is about 20 years since RIF was used to treat ALP in China. Clinical studies showed that this agent was effective against APL. Compared to ATO, RIF is relatively inexpensive and can be taken orally, resulting in reducing the number of hospital days and the treatment cost. However, there is no report comparing treatment outcomes of "ATO + ATRA + chemotherapy" and "RIF + ATRA + chemotherapy" protocols in children with APL so far. For this purpose, therefore, investigators are going to conduct a multicenter and randomized prospective study in children with APL.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

OBJECTIVES:
  • Determine the safety and efficacy of "ATO/RIF + ATRA + less intensive chemotherapy" protocol in children with acute promyelocytic leukemia (APL).

  • Compare the safety,efficacy and treatment cost of "RIF + ATRA + less intensive chemotherapy" with "ATO + ATRA + less intensive chemotherapy" protocol in children with APL. Determine if ATO can be substituted by RIF.

OUTLINE: This is a multicenter and randomized prospective study.

PROJECTED ACCRUAL: A total of 162 patients will be accrued for this study.

Study Design

Study Type:
Interventional
Actual Enrollment :
176 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter and Randomized Prospective Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia
Study Start Date :
Sep 1, 2011
Actual Primary Completion Date :
Oct 1, 2021
Actual Study Completion Date :
Oct 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: ATO and chemotherapy

Induction: ATRA 25mg/m2 d1-CR ≯42 days; ATO 0.16mg/kg d5-CR ≯42 days; mitoxantrone (MA) 10mg/m2 d3, or 7mg/m2 d2-4 (high risk). Consolidation 1: ATRA 25mg/m2 d1-15; MA 10mg/m2 d1-2; Intrathecal injection (IT):Ara-C 15mg (age < 1 year), or 20 mg (1-3 years), or 30 mg ( > 3 years), dexamethasone 2mg. Consolidation 2: ATRA 25mg/m2 d1-15; ATO 0.16mg/kg d1-15; Ara-C 1g/m2 q12h d1-2 (high risk); IT. Consolidation 3: ATRA 25mg/m2 d1-15; ATO 0.16mg/kg d1-15; MA 10mg/m2 d1; Ara-C 1g/m2 q12h d1-2 (high risk); IT. Maintenance: ① ATO 0.16mg/kg.d w1-2; ATRA 25mg/m2.d w1-2; MTX 20mg/m2 qw w3-12; 6MP 50mg/m2 qn w3-12. ② ATRA 25mg/m2.d w1-2; MTX 20mg/m2 qw w3-12; 6MP 50mg/m2 qn w3-12. Rotation between ① and ② until the end of maintenance.

Drug: ATO
Given IV
Other Names:
  • As2O3
  • arsenic trioxide
  • Drug: ATRA
    Given orally
    Other Names:
  • all-trans retinoic acid
  • Drug: mitoxantrone
    Given IV
    Other Names:
  • novantrone
  • Drug: Ara-C
    Given IV
    Other Names:
  • cytarabine
  • cytosine arabinoside
  • Drug: MTX
    Given orally
    Other Names:
  • methotrexate
  • Drug: 6MP
    Given orally
    Other Names:
  • mercaptopurine
  • Other: intrathecal injection
    Ara-C and dexamethasone
    Other Names:
  • IT
  • Experimental: RIF and chemotherapy

    Induction: ATRA 25mg/m2 d1-CR ≯42 days; RIF 0.135/kg d5-CR ≯42 days; mitoxantrone (MA) 10mg/m2 d3, or 7mg/m2 d2-4 (high risk). Consolidation 1: ATRA 25mg/m2 d1-15; MA 10mg/m2 d1-2; Intrathecal injection (IT):Ara-C 15mg (age < 1 year), or 20mg (age 1-3 years), or 30mg (age > 3 years), dexamethasone 2mg. Consolidation 2: ATRA 25mg/m2 d1-15; RIF 0.135/kg d1-15; Ara-C 1g/m2 q12h d1-2 (high risk); IT. Consolidation 3: ATRA 25mg/m2 d1-15; RIF 0.135/kg d1-15; MA 10mg/m2 d1; Ara-C 1g/m2 q12h d1-2 (high risk); IT. Maintenance: ① RIF 0.135/kg.d w1-2; ATRA 25mg/m2.d w1-2; MTX 20mg/m2 qw w3-12; 6MP 50mg/m2 qn w3-12. ② ATRA 25mg/m2.d w1-2; MTX 20mg/m2 qw w3-12; 6MP 50mg/m2 qn w3-12. Rotation between ① and ② until the end of maintenance treatment.

    Drug: RIF
    Given orally
    Other Names:
  • Realgar-Indigo naturalis formula
  • Drug: ATRA
    Given orally
    Other Names:
  • all-trans retinoic acid
  • Drug: mitoxantrone
    Given IV
    Other Names:
  • novantrone
  • Drug: Ara-C
    Given IV
    Other Names:
  • cytarabine
  • cytosine arabinoside
  • Drug: MTX
    Given orally
    Other Names:
  • methotrexate
  • Drug: 6MP
    Given orally
    Other Names:
  • mercaptopurine
  • Other: intrathecal injection
    Ara-C and dexamethasone
    Other Names:
  • IT
  • Outcome Measures

    Primary Outcome Measures

    1. event-free survival [5 years]

    Secondary Outcome Measures

    1. hospitalization cost [2 years]

      The cost mainly includes the fees of hospital bed, drugs, therapies and blood products. Time frame: from the beginning of induction therapy to the end of maintenance treatment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 16 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients less than 16 years old with newly diagnosed PML-RARa positive acute promyelocytic leukemia.
    Exclusion Criteria:
    • Patients who have coma, convulsion or paralysis due to intracranial hemorrhage or central nervous system leukemia at diagnosis.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The First Affiliated Hospital of Sun Yat-Sen University Guangzhou Guangdong China 510080

    Sponsors and Collaborators

    • South China Children's Leukemia Group

    Investigators

    • Principal Investigator: Xue-Qun Luo, professor, First Affiliated Hospital, Sun Yat-Sen University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    South China Children's Leukemia Group
    ClinicalTrials.gov Identifier:
    NCT02200978
    Other Study ID Numbers:
    • 2010001
    First Posted:
    Jul 25, 2014
    Last Update Posted:
    May 10, 2022
    Last Verified:
    May 1, 2022

    Study Results

    No Results Posted as of May 10, 2022