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

Overview

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.

Interventions

• Other Evaluation of first line treatment with ATO/ATRA outcome
  Evaluation of first line treatment with ATO/ATRA outcome (o event free survival and overall survival and toxicity) in adult patients with APL.

Primary outcome measures

• Evaluate overall survival of patients diagnosed with APL and treated in first line with ATO/ATRA or ATO/ATRA/Idarubicin (IDA). [Time frame: 36 months]
• Evaluate event free survival of patients diagnosed with APL and treated in first line with ATO/ATRA or ATO/ATRA/Idarubicin (IDA). [Time frame: 36 months]

Secondary outcome measures (4)

• Evaluate complete molecular remission rate at the end of the consolidation treatment. [Time frame: 36 months]
• Evaluate toxicity of the ATO/ATRA scheme (+/- IDA), measured according to type, frequency, severity and relation with the treatment of adverse events. [Time frame: 36 months]
• Record early mortality (within 30 days of admission). [Time frame: Within 30 days of admission]
• Evaluate whether the presence of mutated FLT3 has prognostic value in patients treated with ATRA/ATO. [Time frame: 36 months]

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:

• Patients with a pre-existing diagnosis of Long QT Syndrome
• 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).
• Patients with a history or presence of significant ventricular or atrial tachyarrhythmia (Grade 3-4, CTCAE v5.2017).
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Argentina · 6 centers

• Hospital Italiano de La Plata — La Plata
• Instituto Privado de Hematologia y Hemoterapia — Paraná
• Hospital Escuela de Agudos Dr. Ramón Madariaga — Posadas
• Hospital Descentralizado Dr. Guillermo Rawson — Rawson
• CEMIC — CABA
• FUNDALEU — CABA

Identifiers

NCT: NCT04897490 · GATLA 11-LPA-20

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗