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

AML Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05339204
• Other study ID #: AML-21
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2021
• Est. completion date: February 1, 2026

Study information

• Verified date: April 2022
• Source: National Research Center for Hematology, Russia
• Contact: Irina Lukianova, MD PhD
• Phone: +79653493473
• Email: Irina.donskova99[@]mail.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: February 1, 2026
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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

Related Conditions & MeSH terms

• AML

Intervention

Procedure:
• allo-HSCT
allo-HSCT from any type of donor

Locations

Country	Name	City	State
Russian Federation	National Research Center for Hematology	Moscow

Sponsors (10)

Lead Sponsor

Collaborator

National Research Center for Hematology, Russia

Botkin Hospital, Clinical hospital ?1 of Sverdlovsk region, Federal Research Clinical Center of Federal Medical & Biological Agency, Russia, Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health, Irkutsk regional clinical hospital, winner of the "Mark of the Honor" award, Nizhny Novgorod regional clinical hospital named after N.A.Semashko, Regional Clinical Hospital of Yaroslavl, St. Petersburg State Pavlov Medical University, The Federal State-Financed Scientific Institution Kirov Research Institute of Hematology and Blood T

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival for AML in CR1 with MRD-negativity after first course of chemo		5 years
Primary	Relapse probability		5 years
Secondary	Overall survival		5 years
Secondary	Disease-free survival		5 years