Clinical trial NCT04897490: RWE of 1st Line Treatment With ATO/ATRA for Adult APL
Official title: Real World Evidence of First Line Treatment With Arsenic Trioxide Plus All Trans Retinoic Acid in Adult Patients With Acute Promyelocytic Leukemia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Promyelocytic Leukemia, Adult Acute
Keywords: Acute Promyelocytic Leukemia
ATRA
ATO
IDA
Lead sponsor: Grupo Argentino de Tratamiento de la Leucemia Aguda
Sponsor class: OTHER
First posted: 2021-05-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with APL in first line treatment

Brief summary: This is a multicenter, observational real world clinical trial with prospective follow up that will evaluate the treatment outcome of acute promyelocytic leukemia (APL) patients in the first line with arsenic trioxide and all trans retinoic acid (ATO/ATRA) based regimens in Argentina.

Detailed description: The purpose of this trial is to gather real world evidence of the characteristics of APL patients in Argentina who receive ATO/ATRA based treatment in first line following our national guidelines. The study primary endpoint is to evaluate event free survival and overall survival of patients diagnosed with APL and treated in first line with ATO/ATRA or ATO/ATRA/Idarubicin (IDA) depending on risk category. Secondary endpoints are complete molecular response (CMR) rate, toxicity, early mortality and prognostic significance of FLT3.

Every APL patient diagnosed in our institutions will follow our guidelines with respect to diagnosis procedures. Risk category will depend on white blood cell counts (WBC), where WBC \>10000 will be considered high risk (HR) and \<10000 WBC, low risk (LR).

Patients will receive induction with ATO plus ATRA daily until hematologic remission or for a maximum of 60 days, followed by ATO 5 days/week, 4 weeks on 4 weeks off, for a total of 4 courses and ATRA 2 weeks on and 2 weeks off for a total of 7 courses.

HR patients will receive 2-3 doses of IDA at the beginning of induction. Central nervous system prophylaxis is contemplated for HR pts or those who have SNC bleeding.

Molecular response will be evaluated at the end of consolidation by RQ-PCR. LR patients who achieve CMR will not need to repeat molecular evaluations but HR patients will need RQ-PCR evaluation every 3 months during the first year and every 6 months during the second year.

Eligibility criteria: Inclusion Criteria:

* Patients 18 years or older.
* Signature of the form consent for participation in the study.
* Diagnosis of APL (either primary or secondary) according to the criteria of the World Health Organization (WHO), without prior treatment.
* Identification of the specific genetic alteration of APL by conventional karyotype, fluorescent in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR or RQ-PCR). Identification of the transcript is recommended at the time of diagnosis isoforms: bcr1, bcr2, bcr3 essential to document the therapeutic response: Molecular remission

Exclusion Criteria:

* Presence of other concomitant active malignant tumors that require simultaneous treatment.
* Having received prior treatment for APL.
* Electrocardiogram abnormalities:

  1. Patients with a pre-existing diagnosis of Long QT Syndrome
  2. Patients with a baseline QTc of\> 450msec. The Bazett formula should be used to measure the corrected QT interval (QT interval in msec divided by the square root of the RR interval in msec).
  3. Patients with a history or presence of significant ventricular or atrial tachyarrhythmia (Grade 3-4, CTCAE v5.2017).
  4. Patients with right bundle branch block plus left anterior hemiblock. Bifascicular blocks are excluded.
* ECOG score 4.
* Stage III-IV heart failure.
* Serum creatinine ≥ 2.5 mg / dL (≥ 250 μmol / L) unless due to APL.
* Bilirubin ≥ 2.5 mg / dL, alkaline phosphatase, GPT or GOT\> 3 times the normal limit unless it is for APL.
* Severe psychiatric illness.
* Women who are pregnant or who have decided to continue breastfeeding.

Primary outcomes:
measure: Evaluate overall survival of patients diagnosed with APL and treated in first line with ATO/ATRA or ATO/ATRA/Idarubicin (IDA).
timeFrame: 36 months
measure: Evaluate event free survival of patients diagnosed with APL and treated in first line with ATO/ATRA or ATO/ATRA/Idarubicin (IDA).
timeFrame: 36 months
Secondary outcomes:
measure: Evaluate complete molecular remission rate at the end of the consolidation treatment.
timeFrame: 36 months
measure: Evaluate toxicity of the ATO/ATRA scheme (+/- IDA), measured according to type, frequency, severity and relation with the treatment of adverse events.
timeFrame: 36 months
measure: Record early mortality (within 30 days of admission).
timeFrame: Within 30 days of admission
measure: Evaluate whether the presence of mutated FLT3 has prognostic value in patients treated with ATRA/ATO.
timeFrame: 36 months
Other outcomes:
Locations:
city: Paraná
country: Argentina
facility: Instituto Privado de Hematologia y Hemoterapia
state: Entre Ríos
city: Posadas
country: Argentina
facility: Hospital Escuela de Agudos Dr. Ramón Madariaga
state: Misiones
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
state: Provincia De Buenos Aires
city: Rawson
country: Argentina
facility: Hospital Descentralizado Dr. Guillermo Rawson
state: San Juan
city: Caba
country: Argentina
facility: CEMIC
city: Caba
country: Argentina
facility: FUNDALEU
Study officials:
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: María José Mela Osorio, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: Isolda Fernández, Dr.
role: STUDY_CHAIR
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: Federico Sackmann, Dr.
role: PRINCIPAL_INVESTIGATOR
References: