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

Sponsor

Hospital Universitario Dr. Jose E. Gonzalez (Other)

Overall Status

Recruiting

CT.gov ID

NCT05497310

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Promyelocytic Leukemia	Drug: Arsenic trioxide Drug: all-trans retinoic acid	Phase 1/Phase 2

Detailed Description

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.

We 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Masking Description:

This is an Open label study

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Jul 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Induction with attenuated ATO plus low-dose ATRA 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 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). Other Names: Trisenox Drug: all-trans retinoic acid Patients will receive ATRA 25/mg/m2/day for 28 continuous days without interruption. Other Names: Vesanoid

Arm

Intervention/Treatment

Experimental: Induction with attenuated ATO plus low-dose ATRA

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

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).

Other Names:

Trisenox

Drug: all-trans retinoic acid

Patients will receive ATRA 25/mg/m2/day for 28 continuous days without interruption.

Other Names:

Vesanoid

Outcome Measures

Primary Outcome Measures

Safety of therapy [28 days]
Safety will be defined by the number of patients deceased after 1 induction cycle of 28 days

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)