IMPACT-AML: Randomized Pragmatic Clinical Trial for Relapsed or Refractory AML

National Research Center for Hematology, Russia

Status and phase: Enrolling; Phase 3

Conditions: Early Relapses of Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Treatments: Other: Low intensity therapy; Other: Intensive therapy

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT06418776

IMPACT-AML

Details and patient eligibility

About

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).

Enrollment: 198 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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198 participants in 2 patient groups

Intensive arm

Active Comparator group

Description:

Fit patients who could potentially undergo courses of intensive chemotherapy and are randomized to intensive chemotherapy courses

Treatment:

Other: Intensive therapy

Low-intensive arm

Active Comparator group

Description:

Fit patients who could potentially undergo courses of intensive chemotherapy and are randomized to low intensity courses

Treatment:

Other: Low intensity therapy