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Treatment of Non-high-risk Acute Promyelocytic Leukemia (APL) With Realgar-Indigo Naturalis Formula (RIF)

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ClinicalTrials.gov Identifier: NCT02899169
Recruitment Status : Recruiting
First Posted : September 14, 2016
Last Update Posted : September 28, 2018
Sponsor:
Collaborator:
Tang-Du Hospital
Information provided by (Responsible Party):
First Affiliated Hospital Xi'an Jiaotong University

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.

Condition or disease Intervention/treatment Phase
Acute Promyelocytic Leukemia Drug: Realgar-Indigo naturalis formula Drug: all-trans retinoic acid Drug: Arsenic trioxide Drug: Hydroxyurea Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Non-high-risk Acute Promyelocytic Leukemia With Realgar-Indigo Naturalis Formula (RIF) and All-trans Retinoid Acid (ATRA)
Study Start Date : September 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
Experimental: Oral Realgar-Indigo naturalis formula(RIF) Group
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 formula
Other Name: RIF

Drug: all-trans retinoic acid
Other Names:
  • ATRA
  • Tretinoin

Drug: Hydroxyurea
Active Comparator: Intravenous Arsenic Trioxide(ATO) Group
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 acid
Other Names:
  • ATRA
  • Tretinoin

Drug: Arsenic trioxide
Other Names:
  • ATO
  • Trisenox (R)
  • As2O3

Drug: Hydroxyurea



Primary Outcome Measures :
  1. Disease-free survival (DFS) [ Time Frame: At 2 years ]

Secondary Outcome Measures :
  1. Rate of overall survival (OS) [ Time Frame: At 2 years ]
  2. Event-free survival [ Time Frame: From date of randomization until the date of first documented event, assessed up to 36 months ]
  3. Rate of cumulative incidence of relapse (CIR) [ Time Frame: assessed up to 3 years after randomization ]
  4. Incidence of hematological and non-hematological toxicity [ Time Frame: From date of randomization until 2 years ]
  5. medical expense [ Time Frame: From date of randomization until 2 years ]
  6. Total hospitalization days during therapy [ Time Frame: At 2 years from study entry ]


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Ages Eligible for Study:   14 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02899169


Contacts
Contact: Huaiyu Wang, Dr. 15809207527 whymed@126.com

Locations
China, Shaanxi
First Affiliated Hospital of Xi'an Jiaotong University Recruiting
Xi'an, Shaanxi, China, 710016
Contact: Huaiyu Wang, Dr.    15809207527    whymed@126.com   
Sponsors and Collaborators
First Affiliated Hospital Xi'an Jiaotong University
Tang-Du Hospital
Investigators
Study Chair: Jun Lu, Dr. First Affiliated Hospital Xi'an Jiaotong University

Publications of Results:
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, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner 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.
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, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner 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.

Responsible Party: First Affiliated Hospital Xi'an Jiaotong University
ClinicalTrials.gov Identifier: NCT02899169     History of Changes
Other Study ID Numbers: APL16
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: September 28, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by First Affiliated Hospital Xi'an Jiaotong University:
Acute promyelocytic leukemia
Realgar-Indigo Naturalis Formula
All-trans Retinoic Acid

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Arsenic trioxide
Hydroxyurea
Tretinoin
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Keratolytic Agents
Dermatologic Agents