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

Phase 3

Recruiting

• Conditions: Early Relapses of Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia
• Interventions: Other: Intensive therapy; Other: Low intensity therapy

• Registration Number: NCT06418776
• Lead Sponsor: National Research Center for Hematology, Russia

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-01
• Study First Submitted: 2024-04-09
• Status Verified: 2024-05
• Study First Submitted QC: 2024-05-13
• Last Update Submitted: 2024-05-13
• Study First Posted: 2024-05-17
• Last Update Posted: 2024-05-17
• Primary Completion: 2027-04
• Study Completion: 2029-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 198

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensive arm	Intensive therapy	Fit patients who could potentially undergo courses of intensive chemotherapy and are randomized to intensive chemotherapy courses
Low-intensive arm	Low intensity therapy	Fit patients who could potentially undergo courses of intensive chemotherapy and are randomized to low intensity courses

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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
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
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

Trial Locations

Locations (1)

National Research Center for Hematology; 🇷🇺 Moscow, Russian Federation