Promyelocytic Leukemia
Conditions
Keywords
all-trans retinoic acid, arsenic trioxide, frontline therapy, induction chemotherapy
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.
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. 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.
Interventions
DRUGArsenic 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).
DRUGall-trans retinoic acid
Patients will receive ATRA 25/mg/m2/day for 28 continuous days without interruption.
Sponsors
Hospital Universitario Dr. Jose E. Gonzalez
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an Open label study
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 28 days | Safety will be defined by the number of patients deceased after 1 induction cycle of 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Mexico
Contacts
Primary ContactEdgar Coronado-Alejandro, MD
Backup ContactAndrés Gómez de León, MD
Outcome results
None listed