Clinical trial NCT05497310: Effectiveness and Safety of Therapy Based on Attenuated ATO Plus Low-Dose ATRA in Patients With APL
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Promyelocytic Leukemia
Keywords: all-trans retinoic acid
arsenic trioxide
frontline therapy
induction chemotherapy
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
First posted: 2022-08-11
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 28 days
Secondary outcomes:
measure: Overall response
timeFrame: 28 days
measure: Progression-free survival
timeFrame: 6 months
measure: Event-free survival
timeFrame: 6 months
measure: Rate of treatment discontinuation due to toxicity.
timeFrame: 28 days
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Hopsital Universitario Dr. Jose E. Gonzalez, Centro Universitario contra el Cancer
state: Nuevo Leon
Study officials:
References:
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citation: Jaime-Perez JC, Gonzalez-Leal XJ, Pinzon-Uresti MA, Gomez-De Leon A, Cantu-Rodriguez OG, Gutierrez-Aguirre H, Gomez-Almaguer D. Is There Still a Role for Low-Dose All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia in the Arsenic Trioxide Era? Clin Lymphoma Myeloma Leuk. 2015 Dec;15(12):816-9. doi: 10.1016/j.clml.2015.09.002. Epub 2015 Sep 25.
citation: Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, Morgan YG, Lok J, Grech A, Jones G, Khwaja A, Friis L, McMullin MF, Hunter A, Clark RE, Grimwade D; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1295-305. doi: 10.1016/S1470-2045(15)00193-X. Epub 2015 Sep 14.