Effectiveness and Safety of Therapy Based on Attenuated ATO Plus Low-Dose ATRA in Patients With APL

Study Overview
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Brief Summary
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ATRA is the standard of care for all patients with APL. The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective. In this study we intent to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO.

Detailed Description
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The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic plasma concentrations sufficient to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO alone demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective in inducing similar remission rates and achieving prolonged survival, also demonstrating a reduction in associated toxicities, mainly hepatic and cardiac when using this new scheme. The investigators will conduct a phase 1/2, non-randomized, single center, non-comparative clinical trial to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO which is accessible to a population with limited resources while maintaining acceptable efficacy and safety.

Official Title
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Effectiveness and Safety of Therapy Based on Attenuated Arsenic Trioxide Plus Low Doses of All-trans Retinoic Acid as Remission Induction Therapy in Patients With Acute Promyelocytic Leukemia Phase 1/2 Clinical Trial

Conditions
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Promyelocytic Leukemia

Intervention / Treatment
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* Drug: Arsenic trioxide
* Drug: all-trans retinoic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Both genders new diagnosis of APL Diagnosis of relapsed APL who have not been previously treated with ATO Morphological diagnosis of APL confirmed by PCR or FISH Exclusion Criteria: Poor functional status (ECOG>2) Organic dysfunction (Marshall score ≥2) Pregnancy Heart failure (NYHA III or IV) Renal failure (GFR <30 ml/min/1.72m2) History of ventricular arrhythmias or uncontrolled arrhythmias Acute myocardial infarction, unstable angina, or stable angina in the last six months Uncontrolled active infection Liver disease (Child-Pugh C)

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: A consecutive sample of 15 patients with newly diagnosed or relapsed APL who have not been previously treated with ATO will be prospectively included in this study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction with attenuated ATO plus low-dose ATRA<br>Remission induction therapy will be administrated as ATRA 25/mg/m2/day for 28 continuous days without interruption if APL is suspected. ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses). | Drug: Arsenic trioxide<br>* Patients will receive ATO 0.3mg/kg/day for days 1-5 (5 doses) and then 0.25 mg/kg/day every other day twice a week for the next 3 weeks (6 doses).<br>* Other names: Trisenox;Drug: all-trans retinoic acid<br>* Patients will receive ATRA 25/mg/m2/day for 28 continuous days without interruption.<br>* Other names: Vesanoid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Safety will be defined by the number of patients deceased after 1 induction cycle of 28 days | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response | Overall response rate was definide as partial response plus complete response after 1 | 28 days | 
| Progression-free survival | Time from achievement of complete hematologic remission to relapse | 6 months | 
| Event-free survival | Time from registration to induction failure, relapse, or death. | 6 months | 
| Rate of treatment discontinuation due to toxicity. | Rate of treatment discontinuation due to toxicity. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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all-trans retinoic acid, arsenic trioxide, frontline therapy, induction chemotherapy