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

Hospital Universitario Dr. Jose E. Gonzalez

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Promyelocytic Leukemia

Treatments: Drug: all-trans retinoic acid; Drug: Arsenic trioxide

Study type: Interventional

Funder types: Other

Identifiers

NCT05497310

HE22-00019

Details and patient eligibility

About

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.

Full 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.

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.

Enrollment: 15 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

Induction with attenuated ATO plus low-dose ATRA

Experimental group

Description:

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).

Treatment:

Drug: all-trans retinoic acid

Drug: Arsenic trioxide