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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Treatment of Non-high-risk Acute Promyelocytic Leukemia With Realgar-Indigo Naturalis Formula (RIF) and All-trans Retinoid Acid (ATRA)

Conditions
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Acute Promyelocytic Leukemia

Intervention / Treatment
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* Drug: Realgar-Indigo naturalis formula
* Drug: all-trans retinoic acid
* Drug: Arsenic trioxide
* Drug: Hydroxyurea


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 70 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 |
| --- | --- |
| Experimental: Oral Realgar-Indigo naturalis formula(RIF) Group<br>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<br> <br> * Other names: RIF;Drug: all-trans retinoic acid<br> <br> * Other names: Tretinoin;Drug: Hydroxyurea<br> <br> |
| Active Comparator: Intravenous Arsenic Trioxide(ATO) Group<br>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<br> <br> * Other names: Tretinoin;Drug: Arsenic trioxide<br> <br> * Other names: As2O3;Drug: Hydroxyurea<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) |  | At 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Total hospitalization days during therapy |  | At 2 years from study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute promyelocytic leukemia, Realgar-Indigo Naturalis Formula, All-trans Retinoic Acid