NCT02899169

Brief Summary

The investigators design a multicenter randomized controlled trial to prove that RIF plus ATRA is possibly superior to ATO plus ATRA as consolidation and maintenance treatment for the patients with non-high-risk APL.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
110

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Sep 2016

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2016

Completed
3 days until next milestone

First Submitted

Initial submission to the registry

September 4, 2016

Completed
10 days until next milestone

First Posted

Study publicly available on registry

September 14, 2016

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2022

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2022

Completed
Last Updated

September 8, 2021

Status Verified

August 1, 2021

Enrollment Period

6 years

First QC Date

September 4, 2016

Last Update Submit

August 31, 2021

Conditions

Acute Promyelocytic Leukemia

Keywords

Acute promyelocytic leukemiaRealgar-Indigo Naturalis FormulaAll-trans Retinoic Acid

Outcome Measures

Primary Outcomes (1)

  • Disease-free survival (DFS)

    At 2 years

Secondary Outcomes (6)

  • Rate of overall survival (OS)

    At 2 years

  • Event-free survival

    From date of randomization until the date of first documented event, assessed up to 36 months

  • Rate of cumulative incidence of relapse (CIR)

    assessed up to 3 years after randomization

  • Incidence of hematological and non-hematological toxicity

    From date of randomization until 2 years

  • medical expense

    From date of randomization until 2 years

  • +1 more secondary outcomes

Study Arms (2)

Oral Realgar-Indigo naturalis formula(RIF) Group

EXPERIMENTAL

Induction therapy: ATO and ATRA, which will maintain until complete hematologic remission. Hydroxyurea should be administrated until WBC count decrease \<10x109/L. Consolidation therapy: RIF（60mg/kg/d) and ATRA 4 weeks on and 2 weeks off, until the fusion gene expression is negative. Maintenance therapy: RIF and ATRA 2 weeks on and 2 weeks off for a total of 6 courses.

Drug: Realgar-Indigo naturalis formulaDrug: all-trans retinoic acidDrug: Hydroxyurea

Intravenous Arsenic Trioxide(ATO) Group

ACTIVE COMPARATOR

Induction therapy: ATO and ATRA, which will maintain until complete hematologic remission. Hydroxyurea should be administrated until WBC count decrease \<10x109/L. Consolidation therapy: ATO and ATRA 4 weeks on and 2 weeks off, until the fusion gene expression is negative. Maintenance therapy: ATO and ATRA 2 weeks on and 2 weeks off for a total of 6 courses.

Drug: all-trans retinoic acidDrug: Arsenic trioxideDrug: Hydroxyurea

Interventions

Realgar-Indigo naturalis formulaDRUG
Also known as: RIF
Oral Realgar-Indigo naturalis formula(RIF) Group
all-trans retinoic acidDRUG
Also known as: ATRA, Tretinoin
Intravenous Arsenic Trioxide(ATO) GroupOral Realgar-Indigo naturalis formula(RIF) Group
Arsenic trioxideDRUG
Also known as: ATO, Trisenox (R), As2O3
Intravenous Arsenic Trioxide(ATO) Group
HydroxyureaDRUG
Intravenous Arsenic Trioxide(ATO) GroupOral Realgar-Indigo naturalis formula(RIF) Group

Eligibility Criteria

Age14 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • age 14 to 70 years
  • Newly diagnosed APL with t(15;17)(q22;q12)
  • Before treatment the Peripheral blood white blood cell count≤10×109/L
  • Patients who can complete the entire treatment process
  • Patients or their families signed written informed consent

You may not qualify if:

  • Be allergic to the drug ingredient, the supplementary material or the allergic constitution person
  • Cardiac insufficiency, renal insufficiency, significant arrhythmias, EKG abnormalities or other important organ dysfunction
  • Combined with other malignant tumors
  • Pregnant and lactating women
  • Participants in other drug trials in the last 3 months
  • Suffering from mental illness or other circumstances which unable to carry out the plan
  • Other patients who were not suitable for the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710016, China

RECRUITING

Related Publications (6)

  • Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lubbert M, Hanel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Dohner K, Sauer M, Ganser A, Amadori S, Mandelli F, Dohner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874.

    PMID: 23841729RESULT

  • Zhu HH, Wu DP, Jin J, Li JY, Ma J, Wang JX, Jiang H, Chen SJ, Huang XJ. Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol. 2013 Nov 20;31(33):4215-21. doi: 10.1200/JCO.2013.48.8312. Epub 2013 Oct 14.

    PMID: 24127444RESULT

  • Zhu HH, Huang XJ. Oral arsenic and retinoic acid for non-high-risk acute promyelocytic leukemia. N Engl J Med. 2014 Dec 4;371(23):2239-41. doi: 10.1056/NEJMc1412035. No abstract available.

    PMID: 25470713RESULT

  • Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lubbert M, Brandts CH, Hanel M, Rollig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial. J Clin Oncol. 2017 Feb 20;35(6):605-612. doi: 10.1200/JCO.2016.67.1982. Epub 2016 Oct 31.

    PMID: 27400939RESULT

  • Chen S, Qin W, Lu X, Liu L, Zheng Y, Lu X, Wang X, Zhang X, Gong S, Wei S, Zhang H, Ding H, Seifollah R, Li J, Zhang H, Wu D, Abiona O, He P, Zhang R, Wald D, Wang H. Arsenic trioxide versus Realgar-Indigo naturalis formula in non-high-risk acute promyelocytic leukemia: a multicenter, randomized trial. Haematologica. 2025 Mar 1;110(3):621-628. doi: 10.3324/haematol.2024.285905.

    PMID: 39506905DERIVED

  • Zhang X, Liu L, Yao Y, Gong S, Wang M, Xi J, Chen L, Wei S, Zhang H, Zhao C, Wang H. Treatment of non-high-risk acute promyelocytic leukemia with realgar-indigo naturalis formula (RIF) and all-trans retinoid acid (ATRA): study protocol for a randomized controlled trial. Trials. 2020 Jan 2;21(1):7. doi: 10.1186/s13063-019-3983-2.

    PMID: 31898521DERIVED

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

TretinoinArsenic TrioxideHydroxyurea

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, AcuteLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Vitamin ARetinoidsCarotenoidsPolyenesAlkenesHydrocarbons, AcyclicHydrocarbonsOrganic ChemicalsCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicTerpenesDiterpenesPigments, BiologicalBiological FactorsArsenicalsInorganic ChemicalsOxidesOxygen CompoundsUreaAmides

Study Officials

  • Huaiyu Wang, Dr.

    First Affiliated Hospital Xi'an Jiaotong University

    STUDY CHAIR

Central Study Contacts

Huaiyu Wang, Dr.

CONTACT

15809207527whymed@126.com

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 4, 2016

First Posted

September 14, 2016

Study Start

September 1, 2016

Primary Completion

September 1, 2022

Study Completion

November 1, 2022

Last Updated

September 8, 2021

Record last verified: 2021-08

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)