A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia

Brief Title

A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia

Official Title

A Multicenter and Randomized Prospective Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia

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.
    

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 Phase

Phase 4

Study Type

Interventional

Primary Outcome

event-free survival

Secondary Outcome

 hospitalization cost

Condition

Childhood Acute Promyelocytic Leukemia

Intervention

ATO

Study Arms / Comparison Groups

 ATO and chemotherapy

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

176

Start Date

September 2011

Completion Date

October 2021

Primary Completion Date

October 2021

Eligibility Criteria

        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.
      

Gender

All

Ages

N/A - 16 Years

Accepts Healthy Volunteers

No

Contacts

Xue-Qun Luo, professor, , 

Location Countries

China

Location Countries

China

NCT ID

NCT02200978

Organization ID

2010001

Responsible Party

Sponsor

Study Sponsor

South China Children's Leukemia Group

Study Sponsor

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

Verification Date

May 2022