Clinical trial NCT05127798: RWE of 1st Line Treatment in Adults With AML From 18 to 70 Years Old.
Official title: Real World Evidence of First Line Treatment With Intensive Chemotherapy in Adult Patients With Acute Myeloid Leukemia From 18 to 70 Years Old
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Myeloid Leukemia, Adult
Keywords: Acute Myeloid Leukemia
Lead sponsor: Grupo Argentino de Tratamiento de la Leucemia Aguda
Sponsor class: OTHER
First posted: 2021-11-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients between 18 and 70 years old with AML 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 Myeloid Leukemia (AML) patients in the first line with intensive chemotherapy based regimens in Argentina.

Detailed description: The purpose of this trial is to gather real world evidence of the characteristics of AML patients in Argentina who receive intensive chemotherapy based treatment in first line following our national guidelines. The study primary endpoint is to evaluate event free survival (EFS) and overall survival (OS) of patients diagnosed with AML and treated in first line with intensive chemotherapy combined with different consolidation modalities depending on risk category. Secondary endpoints are to evaluate EFS and OS according to: cytogenetic and molecular classification, measurable residual disease (MRD) (by flow cytometry) post induction. Assess treatment-related mortality and limitations in completing treatment due to toxicity. Evaluate the role of allogeneic stem cell transplantation in terms of EFS in intermediate and adverse risk patients.

Every AML patient diagnosed in our institutions will follow our guidelines with respect to diagnosis procedures. Risk category will depend on molecular and cytogenetic features according to European Leukemia net 2017 risk stratification.

All patients will receive induction with 7+3 scheme; if CR is not met induction will be followed by a reinduction with FLAG-IDA. According to post induction remission status and risk assessment, consolidation will consist of three courses of cytarabine (2g/m2) + daunorubicin (60mg/m2) for low risk group; or consolidation with cytarabine (2g/m2) + daunorubicin (60mg/m2) followed by allogeneic stem cell transplantation for intermediate and adverse risk groups.

Patients harboring Flt3 mutation will add midostaurin during induction and consolidations: midostaurin 50 mg orally every 12 hours on days 8-21 of each 28-day cycle.

In the cases of Coring Binding Factor AML and NPM1 mutated AML, molecular MRD assessment will be done at the end of consolidations by RQ-PCR and thereafter a follow-up RQ-PCR evaluation every 3 months during the first two years.

Eligibility criteria: Inclusion Criteria:

* Patients 18 years or older.
* Patients with AML (de novo or secondary to MDS or previous treatment) who meet the diagnostic criteria according to WHO 2016 classification.
* Signature of the form consent for participation in the study.

Exclusion Criteria:

* Men and women, \<18 or \>70 years of age.
* Patients with chronic myeloid leukemia blast crisis or transformation to acute leukemia of other myeloproliferative syndromes.
* Patients with relapsed AML.
* Acute promyelocytic leukemia t(15; 17) or variants.
* Absence of written informed consent.
* Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3 that is not due to the disease that motivates the treatment (AML).
* Transplant Comorbidity Index (HCT-CI) \>3.
* Left ventricular ejection fraction \< 40% by echocardiogram (Simpsom).
* Bilirubin, alkaline phosphatase or alanine aminotransferase \> 3 times the upper normal limit not due to AML.
* Serum creatinine ≥ 2.5 mg/dL not due to AML.
* Positive pregnancy test or absence of effective methods of contraception in women of childbearing age.
* Presence of active neoplasia other than AML whose treatment is more urgent at the discretion of the treating physicians.
* Presence of serious psychiatric illness.
* Known history of infection with human immunodeficiency virus (HIV). Active uncontrolled Hepatitis C or Active uncontrolled Hepatitis B.
* Any other condition, such as age or associated pathology that contraindicates treatment with intensive chemotherapy, especially with anthracyclines. Any patient who does not meet the inclusion and exclusion criteria for treatment with intensive chemotherapy may be evaluated on an individual basis if it is considered that they could still benefit from this treatment.

Primary outcomes:
measure: Evaluate the Overall Survival of patients diagnosed with primary or secondary AML between 18 and 70 years of age treated in first line with intensive chemotherapy regimens and risk-adapted consolidation.
timeFrame: 36 months
measure: Evaluate the Event Free Survival of patients diagnosed with primary or secondary AML between 18 and 70 years of age treated in first line with intensive chemotherapy regimens and risk-adapted consolidation.
timeFrame: 36 months
Secondary outcomes:
measure: Evaluate the Complete Remission Rate with negative measurable residual disease (MRD) determined by CMF at the end of induction treatment.
timeFrame: 36 months
measure: Evaluate the toxicity of the scheme measured by type, frequency, severity and relation to treatment of adverse events.
timeFrame: 36 months
measure: Evaluate treatment-related mortality (within 30 days of admission).
timeFrame: Within 30 days of admission
measure: Evaluate the role of measurable residual disease (MRD) in terms of EFS prior to each consolidation.
timeFrame: 36 months
measure: Evaluate the role of allogeneic stem cell transplantation in terms of EFS in intermediate and adverse risk patients.
timeFrame: 36 months
Other outcomes:
Locations:
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
state: Buenos Aires
city: Caba
country: Argentina
facility: FUNDALEU
Study officials:
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: Maria Jose Mela Osorio, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: Hernan Dick, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: Isolda Fernandez, Dr.
role: STUDY_CHAIR
References: