Refractory Acute Myeloid Leukemia, Early Relapses of Acute Myeloid Leukemia
Conditions
Keywords
Acute myeloid leukemia, Relapse of AML, Refractory AML, Allogeneic Stem Cell Transplantation
Brief summary
The primary objective is to evaluate the efficacy and toxicity of high versus low intensity therapy options in patients with refractory forms and early relapses of acute myeloid leukemia (R/R AML) who are scheduled for allogeneic hematopoietic stem cell transplantation (alloHSCT).
Interventions
OTHERIntensive therapy
Intensive chemotherapy courses (MEC, FLAG, FLAG-Ida, FLAG-Mito)
OTHERLow intensity therapy
Low intensity therapy (Aza+Ven, Dac+Ven, LDARA-C+Ven)
Sponsors
St. Petersburg State Pavlov Medical University
Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
National Research Center for Hematology, Russia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients who could potentially undergo courses of intensive chemotherapy (fit) are randomisedrandomized into two arms: * Arm 1 - intensive chemotherapy courses (MEC, FLAG, FLAG-Ida, FLAG-Mito) * Arm 2 - low intensity therapy (Aza/Dac/LDARA-C + Ven) Randomization determines the intensity of the program, but not the specific therapeutic regimen. The treatment regimen is selected by the investigators based on accepted clinical practice, the availability of appropriate drugs at the participating centers, etc., after randomization. If a patient has FLT3 gene mutations, one of the available kinase inhibitors must be added to therapy: midostaurin, gilteritinib, sorafenib. If remission of the AML has been achieved, patients in both groups undergo alloHSCT as soon as possible.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years; * Primary refractory AML; * Early relapsed AML; * A signed informed consent to participate in the study.
Exclusion criteria
* Late relapsed AML; * Isolated extramedullary relapse; * MRD relapse without development of bone marrow relapse of AML; * Acute promyelocytic leukemia; * Previous refractoriness or loss of response during ongoing venetoclax therapy; * Previous alloHSCT; * Pregnancy and/or lactation period; * Refusal of patients with preserved reproductive potential to use highly effective methods of contraception during the period of participation in the study; * Lack of signed informed consent to participate in the study; * Failure of the subject to follow the study protocol; * Participation in any other clinical trial; * Uncontrolled infectious complications; * ECOG ≥ 3; * History of other malignancies within the past 3 years, excluding squamous cell and basal cell skin cancers, carcinoma in situ of the cervix, breast, or other non-invasive malignancies, which, in the opinion of the investigator, are considered adequately treated and have a minimal risk of recurrence within 3 years; * Chronic kidney disease with GFR ≤ 30 ml/min/1.73 m2 (according to the CKD-EPI Creatinine Equation); * Severe cardiac pathology: 1. uncontrolled arterial hypertension; 2. stable angina III-IV functional classes; 3. unstable angina and/or myocardial infarction less than 6 months before inclusion in the study; 4. heart failure stages IIb-III, NYHA functional classes III-IV 5. uncontrolled cardiac rhythm disturbances (≥ 2 grade CTCAE 5.0) or clinically significant ECG abnormalities. * Cirrhosis classes B-C according to the Child-Pugh classification * Increased liver function tests above the following values: 1. Total bilirubin \> 1,5 above the normal range; 2. AST, ALT \> 10 above the normal range. * Major surgical interventions underwent less than 14 days before inclusion in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival of patients with R/R AML depending on the use of high or low intensity therapy exposure before alloHSCT | 2 years | Evaluation method: Kaplan-Meier curves and log-rank test, censored for transplantation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Probability of achieving a response (CR, CR with incomplete hematological recovery, morphologic leukemia- free state, partial remission) in patients with R/R AML, depending on the use of high or low intensity treatment regimens | 3 months | Assessment method: Chi-square test |
| Cumulative incidence of alloHSCT in patients with R/R AML, depending on the use of high or low intensity treatment regimens | 2 years | Evaluation method: cumulative frequency curves and Gray's test |
| Toxicity of high versus low intensity regimens | 3 months | Evaluation method: Chi-square test, parametric/nonparametric tests for means Variables to be evaluated: 1. Maximum degree and duration of neutropenia and/or thrombocytopenia; 2. Development of uncontrolled/life-threatening infectious complications; 3. Development of life-threatening hemorrhagic complications; 4. Development of severe organ failure. |
| OS over the entire duration of the study, including follow-up after alloHSCT | 2 years | Evaluation method: Kaplan-Meier curves and log-rank test |
| Probability of achieving CR in patients with R/R AML, depending on the use of high or low intensity treatment regimens | 3 months | Assessment method: Chi-square test |
| Relapse incidence in patients with R/R AML when achieving remission before performing alloHSCT, depending on the use of high or low intensity treatment regimens | 2 years | Evaluation method: cumulative frequency curves and Gray's test |
| EFS of patients with R/R AML depending on the use of high or low intensity regimens, regardless of alloHSCT | 2 years | Evaluation method: Farington-Manning test, not censored for transplantation |
| Statistics on discontinued participation in the protocol and premature withdrawal from the study | 2 years | Assessment method: Chi-square test |
| RFS in patients with R/R AML when achieving remission before alloHSCT, depending on the use of high or low intensity treatment regimens | 2 years | Evaluation method: Kaplan-Meier curves and log-rank test |
Countries
Russia
Contacts
Primary ContactAnastasia Kashlakova, MD
Backup ContactElena Parovichnikova, MD
Outcome results
None listed