A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia
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:
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Determine the safety and efficacy of "ATO/RIF + ATRA + less intensive chemotherapy" protocol in children with acute promyelocytic leukemia (APL).
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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
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:
Drug: ATRA
Given orally
Other Names:
Drug: mitoxantrone
Given IV
Other Names:
Drug: Ara-C
Given IV
Other Names:
Drug: MTX
Given orally
Other Names:
Drug: 6MP
Given orally
Other Names:
Other: intrathecal injection
Ara-C and dexamethasone
Other Names:
|
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:
Drug: ATRA
Given orally
Other Names:
Drug: mitoxantrone
Given IV
Other Names:
Drug: Ara-C
Given IV
Other Names:
Drug: MTX
Given orally
Other Names:
Drug: 6MP
Given orally
Other Names:
Other: intrathecal injection
Ara-C and dexamethasone
Other Names:
|
Outcome Measures
Primary Outcome Measures
- event-free survival [5 years]
Secondary Outcome Measures
- 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
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
- 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.
- 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.
- 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 Thé 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. Epub 2004 Mar 24.
- 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.
- 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.
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