search
Back to results

A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia

Primary Purpose

Childhood Acute Promyelocytic Leukemia

Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
ATO
RIF
ATRA
mitoxantrone
Ara-C
MTX
6MP
intrathecal injection
Sponsored by
South China Children's Leukemia Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Childhood Acute Promyelocytic Leukemia

Eligibility Criteria

undefined - 16 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The First Affiliated Hospital of Sun Yat-Sen University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

ATO and chemotherapy

RIF and chemotherapy

Arm 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.

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.

Outcomes

Primary Outcome Measures

event-free survival

Secondary Outcome Measures

hospitalization cost
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.

Full Information

First Posted
February 8, 2014
Last Updated
May 7, 2022
Sponsor
South China Children's Leukemia Group
search

1. Study Identification

Unique Protocol Identification Number
NCT02200978
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
October 2021 (Actual)
Study Completion Date
October 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
South China Children's Leukemia Group

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Childhood Acute Promyelocytic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
176 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ATO and chemotherapy
Arm Type
Active Comparator
Arm 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.
Arm Title
RIF and chemotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ATO
Other Intervention Name(s)
As2O3, arsenic trioxide
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
RIF
Other Intervention Name(s)
Realgar-Indigo naturalis formula
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
ATRA
Other Intervention Name(s)
all-trans retinoic acid
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
mitoxantrone
Other Intervention Name(s)
novantrone
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Ara-C
Other Intervention Name(s)
cytarabine, cytosine arabinoside
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
MTX
Other Intervention Name(s)
methotrexate
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
6MP
Other Intervention Name(s)
mercaptopurine
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
intrathecal injection
Other Intervention Name(s)
IT
Intervention Description
Ara-C and dexamethasone
Primary Outcome Measure Information:
Title
event-free survival
Time Frame
5 years
Secondary Outcome Measure Information:
Title
hospitalization cost
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xue-Qun Luo, professor
Organizational Affiliation
First Affiliated Hospital, Sun Yat-Sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
15044693
Citation
Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, Shi JY, Zheng PZ, Yan H, Liu YF, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De The H, Wang ZY, Chen SJ, Chen Z. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5328-35. doi: 10.1073/pnas.0400053101. Epub 2004 Mar 24.
Results Reference
background
PubMed Identifier
19225113
Citation
Hu J, Liu YF, Wu CF, Xu F, Shen ZX, Zhu YM, Li JM, Tang W, Zhao WL, Wu W, Sun HP, Chen QS, Chen B, Zhou GB, Zelent A, Waxman S, Wang ZY, Chen SJ, Chen Z. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3342-7. doi: 10.1073/pnas.0813280106. Epub 2009 Feb 18.
Results Reference
background
PubMed Identifier
18344322
Citation
Wang L, Zhou GB, Liu P, Song JH, Liang Y, Yan XJ, Xu F, Wang BS, Mao JH, Shen ZX, Chen SJ, Chen Z. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4826-31. doi: 10.1073/pnas.0712365105. Epub 2008 Mar 14.
Results Reference
background
PubMed Identifier
19954593
Citation
Xiang Y, Wang XB, Sun SJ, Guo AX, Wei AH, Cheng YB, Huang SL. [Compound huangdai tablet as induction therapy for 193 patients with acute promyelocytic leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2009 Jul;30(7):440-2. Chinese.
Results Reference
background
PubMed Identifier
19422024
Citation
Luo XQ, Ke ZY, Huang LB, Guan XQ, Zhang YC, Zhang XL. Improved outcome for Chinese children with acute promyelocytic leukemia: a comparison of two protocols. Pediatr Blood Cancer. 2009 Sep;53(3):325-8. doi: 10.1002/pbc.22042.
Results Reference
background
PubMed Identifier
35760920
Citation
Liao LH, Chen YQ, Huang DP, Wang LN, Ye ZL, Yang LH, Mai HR, Li Y, Liang C, Luo JS, Wang LN, Luo XQ, Tang YL, Zhang XL, Huang LB. The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia. Cancer Chemother Pharmacol. 2022 Jul;90(1):45-52. doi: 10.1007/s00280-022-04449-9. Epub 2022 Jun 27.
Results Reference
derived

Learn more about this trial

A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia

We'll reach out to this number within 24 hrs