The Role of Allo-HSCT in MRD-negative Patients With AML Under the Age of 60 Years in the First Complete Remission

Study Overview
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Brief Summary
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Depending on the variant of the disease, patients are divided into 3 groups: A, B and C. Group A include patients with acute myeloid leukemia (AML) inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11, group B - AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1, AML with normal karyotype with or without gene mutations (FLT3, NPM1, CEBPa) regardless of the allele ratio, and also AML with cytogenetic abnormalities not classified as those within groups A/C, group C - AML with myelodysplasia-related changes. Patients from group A receive treatment according to the scheme: 2 courses 7+3, 2 courses FLAG, then - 6 courses of maintenance therapy according to the scheme 5+5. Patients from group B are given one course of 7+3. After that, their minimal residual disease (MRD) status is assessed. In case MRD negativity is achieved after the 1st course of 7 +3, randomization is carried out: branch 1 - therapy is similar to therapy for patients from group A (4 courses of induction and consolidation + 6 courses of maintenance chemotherapy (CT), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not planned), branch 2 - performing allo-HSCT should be done as soon as possible (before the start of maintenance CT is most desirable). If MRD negativity is not achieved after the 1st course of 7+3, the patient is given CT according to the standard program, followed by mandatory allo-HSCT. Patients from group C are treated either according to the Aza-Ida-Ara-C scheme, or according to the Ven-DAC /AZA scheme, followed by mandatory allo-HSCT.

Detailed Description
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7+3 regimen: Cytarabine 200 mg/m2 (IV continuous infusion over 24 hours), days 1-7 Daunorubicin 60 mg/m2 (IV bolus), days 1-3 FLAG regimen: Fludarabine 25 mg/m2 (IV in 30 minutes), days 1-5 Cytarabine 1500 mg/m2 (IV in 3 hours), days 1-5 Granulocyte colony-stimulating factor 5 mcg/kg (subcutaneous injection), from day 6 until regression of cytopenia Aza-Ida-Ara-C regimen: Azacitidine 75 mg/m2 (subcutaneous injection), days 1-3 Idarubicin 3 mg/m2 (IV bolus), days 4-10 Cytarabine 15 mg/m2 twice a day (subcutaneous injection), days 4-17 Ven-DAC/AZA Venetoclax 400 mg once daily (PO), days 1-28 Either Azacitidine or Decitabine Azacitidine 75 mg/m2 (subcutaneous injection), days 1-7 Decitabine 20 mg/m2 (IV in 60 minutes). days 1-5 5+5 regimen Cytarabine 50 mg/m2 twice a day (subcutaneous injection), days 1-5 Mercaptopurine 30 mg/m2 twice a day (PO), days 1-5

Official Title
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Prospective Multicenter Randomized Controlled Clinical Trial for Evaluation the Role of Allo-HSCT in the First Complete Remission, MRD-negative After the First Course, in Patients With AML Under the Age of 60 Years

Conditions
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AML

Intervention / Treatment
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* Procedure: allo-HSCT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed, previously untreated AML; Age from 18 to 59 years; Somatic status - ECOG < 3. Exclusion Criteria: previous chemotherapy for AML; pregnancy; relapses and refractory forms of AML; acute promyelocytic leukemia; blast crisis of chronic myeloid leukemia; de novo AML with t(9;22); AML transformed from MDS or MPN after treatment, for which a different protocol is provided; Blastoid plasmacytoid dendritic cell neoplasia (with the exception of cases when a small population of plasmacytoid dendritic progenitors is detected in the leukemic neoplasia). Undifferentiated acute leukemia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: allo-HSCT<br>Patients with AML in CR1, MRD-negative after first course recieve allo-HSCT | Procedure: allo-HSCT<br>* allo-HSCT from any type of donor<br>|
| Active Comparator: Chemo<br>Patients with AML in CR1, MRD-negative after first course continue chemotherapy | Procedure: allo-HSCT<br>* allo-HSCT from any type of donor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival for AML in CR1 with MRD-negativity after first course of chemo |  | 5 years | 
| Relapse probability |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years | 
| Disease-free survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, MRD, allo-HSCT, CR1, adult