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

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

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.

Study Overview

• Status: Recruiting
• Conditions: AML
• Intervention / Treatment: Procedure: allo-HSCT

Detailed Description

"7+3" regimen:

1. Cytarabine 200 mg/m2 (IV continuous infusion over 24 hours), days 1-7
2. Daunorubicin 60 mg/m2 (IV bolus), days 1-3

"FLAG" regimen:

1. Fludarabine 25 mg/m2 (IV in 30 minutes), days 1-5
2. Cytarabine 1500 mg/m2 (IV in 3 hours), days 1-5
3. Granulocyte colony-stimulating factor 5 mcg/kg (subcutaneous injection), from day 6 until regression of cytopenia

"Aza-Ida-Ara-C" regimen:

1. Azacitidine 75 mg/m2 (subcutaneous injection), days 1-3
2. Idarubicin 3 mg/m2 (IV bolus), days 4-10
3. Cytarabine 15 mg/m2 twice a day (subcutaneous injection), days 4-17

"Ven-DAC/AZA"

1. Venetoclax 400 mg once daily (PO), days 1-28
2. 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

1. Cytarabine 50 mg/m2 twice a day (subcutaneous injection), days 1-5
2. Mercaptopurine 30 mg/m2 twice a day (PO), days 1-5

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Irina Lukianova, MD PhD; Phone Number: +79653493473; Email: Irina.donskova99@mail.ru
• Study Contact Backup: Name: Anastasia Kashlakova, MD; Phone Number: +74956124592; Email: salvatorvaltz@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • National Research Center for Hematology
    • Contact: Elena Parovichnikova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Newly diagnosed, previously untreated AML;
2. Age from 18 to 59 years;
3. Somatic status - ECOG < 3.

Exclusion Criteria:

1. previous chemotherapy for AML;
2. pregnancy;
3. relapses and refractory forms of AML;
4. acute promyelocytic leukemia;
5. blast crisis of chronic myeloid leukemia;
6. de novo AML with t(9;22);
7. AML transformed from MDS or MPN after treatment, for which a different protocol is provided;
8. Blastoid plasmacytoid dendritic cell neoplasia (with the exception of cases when a small population of plasmacytoid dendritic progenitors is detected in the leukemic neoplasia).
9. Undifferentiated acute leukemia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Research Center for Hematology, Russia
• Collaborators: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia; St. Petersburg State Pavlov Medical University; Botkin Hospital; Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health; Regional Clinical Hospital of Yaroslavl; Nizhny Novgorod regional clinical hospital named after N.A.Semashko; Clinical hospital №1 of Sverdlovsk region; Irkutsk regional clinical hospital, winner of the "Mark of the Honor" award; The Federal State-Financed Scientific Institution Kirov Research Institute of Hematology and Blood T

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Anticipated): February 1, 2026
• Study Completion (Anticipated): February 1, 2026

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Actual): April 21, 2022
• Last Update Submitted That Met QC Criteria: April 14, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: AML, MRD, allo-HSCT, CR1, adult
• Other Study ID Numbers: AML-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

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