Clinical trial NCT06418776: IMPACT-AML: Randomized Pragmatic Clinical Trial for Relapsed or Refractory AML
Official title: A Prospective Multicenter Randomized Clinical Trial on the Treatment of Patients With Refractory or Early Relapses of Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Refractory Acute Myeloid Leukemia
Early Relapses of Acute Myeloid Leukemia
Keywords: Acute myeloid leukemia
Relapse of AML
Refractory AML
Allogeneic Stem Cell Transplantation
Lead sponsor: National Research Center for Hematology, Russia
Sponsor class: NETWORK
Collaborators: name: St. Petersburg State Pavlov Medical University
name: Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
First posted: 2024-05-17
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Event-free survival of patients with R/R AML depending on the use of high or low intensity therapy exposure before alloHSCT
timeFrame: 2 years
Secondary outcomes:
measure: Probability of achieving CR in patients with R/R AML, depending on the use of high or low intensity treatment regimens
timeFrame: 3 months
measure: 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
timeFrame: 3 months
measure: Cumulative incidence of alloHSCT in patients with R/R AML, depending on the use of high or low intensity treatment regimens
timeFrame: 2 years
measure: Toxicity of high versus low intensity regimens
timeFrame: 3 months
measure: OS over the entire duration of the study, including follow-up after alloHSCT
timeFrame: 2 years
measure: RFS in patients with R/R AML when achieving remission before alloHSCT, depending on the use of high or low intensity treatment regimens
timeFrame: 2 years
measure: 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
timeFrame: 2 years
measure: EFS of patients with R/R AML depending on the use of high or low intensity regimens, regardless of alloHSCT
timeFrame: 2 years
measure: Statistics on discontinued participation in the protocol and premature withdrawal from the study
timeFrame: 2 years
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: National Research Center for Hematology
Study officials:
References: