Clinical trial NCT02899169: Treatment of Non-high-risk Acute Promyelocytic Leukemia (APL) With Realgar-Indigo Naturalis Formula (RIF)
Official title: Treatment of Non-high-risk Acute Promyelocytic Leukemia With Realgar-Indigo Naturalis Formula (RIF) and All-trans Retinoid Acid (ATRA)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Acute Promyelocytic Leukemia
Keywords: Acute promyelocytic leukemia
Realgar-Indigo Naturalis Formula
All-trans Retinoic Acid
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Tang-Du Hospital
First posted: 2016-09-14
Enrollment: 110
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) which accounts for 10-15% of acute myeloid leukemia. It is characterized by the PML-RARA fusion gene generated by the t(15;17)(q22;q21) chromosomal translocation. The application of ATRA and ATO, make APL from highly fatal to highly curable. APL0406 study proves that ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with non-high-risk APL. Now, the arsenic trioxide has already became the based regimen as targeted first-line treatment without chemotherapy. A study shows that oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as maintenance treatment of APL. 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. Application of oral RIF decrease the total hospitalization days.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Disease-free survival (DFS)
timeFrame: At 2 years
Secondary outcomes:
measure: Rate of overall survival (OS)
timeFrame: At 2 years
measure: Event-free survival
timeFrame: From date of randomization until the date of first documented event, assessed up to 36 months
measure: Rate of cumulative incidence of relapse (CIR)
timeFrame: assessed up to 3 years after randomization
measure: Incidence of hematological and non-hematological toxicity
timeFrame: From date of randomization until 2 years
measure: medical expense
timeFrame: From date of randomization until 2 years
measure: Total hospitalization days during therapy
timeFrame: At 2 years from study entry
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Huaiyu Wang, Dr.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.