RWE of 1st Line Treatment With ATO/ATRA for Adult APL

Real World Evidence of First Line Treatment With Arsenic Trioxide Plus All Trans Retinoic Acid in Adult Patients With Acute Promyelocytic Leukemia

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.

Study Overview

• Status: Recruiting
• Conditions: Promyelocytic Leukemia, Adult Acute
• Intervention / Treatment: Other: Evaluation of first line treatment with ATO/ATRA outcome

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.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Federico Sackmann, Dr.; Phone Number: +5491149720765; Email: fsackmann@fundaleu.org.ar
• Study Contact Backup: Name: Paula Freigeiro; Phone Number: +5491140470052; Email: gatla.ar@gmail.com

Study Locations

• Argentina
  • Caba, Argentina
    • Recruiting
    • CEMIC
    • Contact: Nicolás Cazap, Dr.
  • Caba, Argentina
    • Recruiting
    • Fundaleu
    • Contact: Federico Sackmann, Dr.
  • Entre Ríos
    • Paraná, Entre Ríos, Argentina
      • Recruiting
      • Instituto Privado de Hematologia y Hemoterapia
      • Contact: Pedro Negri Aranguren, Dr.
      • Principal Investigator: Florencia Negri Aranguren, Dr.
  • Misiones
    • Posadas, Misiones, Argentina
      • Recruiting
      • Hospital Escuela de Agudos Dr. Ramón Madariaga
      • Contact: Diego Wolhein, Dr.
  • Provincia De Buenos Aires
    • La Plata, Provincia De Buenos Aires, Argentina
      • Recruiting
      • Hospital Italiano de La Plata
      • Contact: Hernán Dick, Dr.
  • San Juan
    • Rawson, San Juan, Argentina
      • Recruiting
      • Hospital Descentralizado Dr. Guillermo Rawson
      • Contact: María Celina Vanina, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with APL in first line treatment

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult APL in first line; Patients >/= 18 years old with recent diagnosis of acute promyelocytic leukemia who receive treatment with ATO/ATRA according to our local guidelines. HR patients will receive 2-3 additional doses of idarubicin.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate overall survival of patients diagnosed with APL and treated in first line with ATO/ATRA or ATO/ATRA/Idarubicin (IDA).	Evaluate overall survival of patients >/= 18 years old diagnosed with APL and treated in first line with ATO/ATRA or ATO/ATRA/Idarubicin (IDA) depending on risk category.	36 months
Evaluate event free survival of patients diagnosed with APL and treated in first line with ATO/ATRA or ATO/ATRA/Idarubicin (IDA).	Evaluate event free survival of patients >/= 18 years old diagnosed with APL and treated in first line with ATO/ATRA or ATO/ATRA/Idarubicin (IDA) depending on risk category.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate complete molecular remission rate at the end of the consolidation treatment.		36 months
Evaluate toxicity of the ATO/ATRA scheme (+/- IDA), measured according to type, frequency, severity and relation with the treatment of adverse events.		36 months
Record early mortality (within 30 days of admission).		Within 30 days of admission
Evaluate whether the presence of mutated FLT3 has prognostic value in patients treated with ATRA/ATO.	The prognostic value will be analyzed by comparing rates of complete remission (CR), hematological relapse, molecular relapse, PFS and OS.	36 months

Collaborators and Investigators

• Sponsor: Grupo Argentino de Tratamiento de la Leucemia Aguda
• Investigators: Principal Investigator: María José Mela Osorio, Dr., Grupo Argentino de Tratamiento de la Leucemia Aguda; Study Chair: Isolda Fernández, Dr., Grupo Argentino de Tratamiento de la Leucemia Aguda; Principal Investigator: Federico Sackmann, Dr., Grupo Argentino de Tratamiento de la Leucemia Aguda

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 21, 2021

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: IDA; ATRA; ATO; Acute Promyelocytic Leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia; Leukemia, Promyelocytic, Acute
• Other Study ID Numbers: GATLA 11-LPA-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Share study protocol
• IPD Sharing Time Frame: The data will become available on June 2021, and will remain available until the end of the clinical trial.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No