Cytarabine (Ara-C) in Children With Acute Promyelocytic Leukemia (APL)

Study Overview
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Brief Summary
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Several groups, especially the PETHEMA group (in their LPA96 and 99 trials), obtained low relapse rates in newly diagnosed Acute Promyelocytic Leukemia (APL) patients by combining ll-transretinoic acid (ATRA) and anthracyclines without Ara-C, suggesting that avoiding Ara-C in the chemotherapy of APL reduced treatment toxicity without increasing relapses. While the relapse rate for the children with white blood cell(WBC) counts greater than 10×109/L at presentation were higher than those WBC counts less than 10×109/L (31% and 3.5%,respectively) in the LPA96 and 99 trials. A recent adult randomized trial show that avoiding Ara-C leads to an increased risk of relapse in the APL patients with WBC counts less than 10×109/L. The role of the Ara-C remains controversial. And there are very limited data reported on children with APL so far.

Detailed Description
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Some studies suggest patients with high-risk disease should be treated with intensified doses of anthracycline, or intermediate/ high-dose Ara-C or As2O3 as an early consolidation, so as to decrease the risk of relapse.However, a higher cumulative dose of anthracycline may lead to cardiac toxicity, especially for children. In addition, containing Ara-C will led to more therapy-related toxicity. The benefit to add Ara-C to the schedules is questionable and remains a matter of investigation in children.

Official Title
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Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia in Children: Remission Induction With All-transretinoic Acid (ATRA) and Arsenic Trioxide (As2O3). Consolidation With Daunorubicin(DNR)+Ara-c or DNR Alone.

Conditions
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Leukemia

Intervention / Treatment
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* Drug: DNR:
* Drug: Ara-c


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute Promyelocytic Leukemia (APL) Exclusion Criteria: > 14

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DNR+Ara-c(Ara-C group)<br>patients in this group were treated with DNR+Ara-C in consolidation | Drug: DNR:<br>* DNR：45mg/m2 d1-3<br>Drug: Ara-c<br>* DNR+ARA-C：DNR：45mg/m2 d1-3;Ara-C :1g/m2 d1-3<br>|
| Experimental: DNR(No Ara-C group)<br>patients in this group were treated with DNR alone in consolidation | Drug: DNR:<br>* DNR：45mg/m2 d1-3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Overall Survival of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | We assessed the OS of APL patients when ATRA and ATO were used. The overall survival (OS) durations was calculated from the date of diagnosis to last follow-up or death. | two years | 
| the Event-free Survival (EFS） of APL Patients Treated With Retinoic Acid Receptor Alpha (ATRA) and Arsenic Trioxide (ATO) Based Trial | We assessed the EFS of APL patients treated with retinoic acid receptor alpha (ATRA) and Arsenic Trioxide (ATO) based trial. Event-free survival (EFS) was defined as time from diagnosis to last follow-up or an event (relapse or death). | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Side Effects | Also, we compared the side effect and outcome between the two groups.To assessed whether Ara-C could be omitted when ATO and ATRA were used. | three years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ara-c, As2O3, pediatric, acute