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

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.

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.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: DNR:; Drug: Ara-c

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Tianjin, China, 300020
    • Department of Pediatrics, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, PR China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology & Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute Promyelocytic Leukemia (APL)

Exclusion Criteria:

• > 14

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xiaofan Zhu
• Investigators: Principal Investigator: Xiaofan Zhu, MD, Department of Pediatrics, CAMS&PUMC

Publications and helpful links

General Publications

• Ortega JJ, Madero L, Martin G, Verdeguer A, Garcia P, Parody R, Fuster J, Molines A, Novo A, Deben G, Rodriguez A, Conde E, de la Serna J, Allegue MJ, Capote FJ, Gonzalez JD, Bolufer P, Gonzalez M, Sanz MA; PETHEMA Group. Treatment with all-trans retinoic acid and anthracycline monochemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA Group. J Clin Oncol. 2005 Oct 20;23(30):7632-40. doi: 10.1200/JCO.2005.01.3359.
• Zhang L, Zou Y, Chen Y, Guo Y, Yang W, Chen X, Wang S, Liu X, Ruan M, Zhang J, Liu T, Liu F, Qi B, An W, Ren Y, Chang L, Zhu X. Role of cytarabine in paediatric acute promyelocytic leukemia treated with the combination of all-trans retinoic acid and arsenic trioxide: a randomized controlled trial. BMC Cancer. 2018 Apr 3;18(1):374. doi: 10.1186/s12885-018-4280-2.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2010
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: August 18, 2010
• First Submitted That Met QC Criteria: August 30, 2010
• First Posted (Estimate): August 31, 2010

Study Record Updates

• Last Update Posted (Actual): August 10, 2021
• Last Update Submitted That Met QC Criteria: August 8, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: acute; pediatric; ara-c; As2O3
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia; Leukemia, Promyelocytic, Acute
• Other Study ID Numbers: CCAPL2010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No