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

A Prospective Multicenter Randomized Clinical Trial on the Treatment of Patients With Refractory or Early Relapses of Acute Myeloid Leukemia

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).

Study Overview

• Status: Recruiting
• Conditions: Refractory Acute Myeloid Leukemia; Early Relapses of Acute Myeloid Leukemia
• Intervention / Treatment: Other: Intensive therapy; Other: Low intensity therapy

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anastasia Kashlakova, MD; Phone Number: +79629087553; Email: kashlakova.a.i@gmail.com
• Study Contact Backup: Name: Elena Parovichnikova, MD; Phone Number: +74956122123; Email: parovichnikova.e@blood.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 125167
    • Recruiting
    • National Research Center for Hematology
    • Contact: Elena Parovichnikova, MD; Phone Number: +74956122361; Email: director@blood.ru
    • Contact: Anastasia Kashlakova, MD; Phone Number: +74956124592; Email: kashlakova.a@blood.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intensive arm; Fit patients who could potentially undergo courses of intensive chemotherapy and are randomized to intensive chemotherapy courses	Other: Intensive therapy; Intensive chemotherapy courses (MEC, FLAG, FLAG-Ida, FLAG-Mito)
Active Comparator: Low-intensive arm; Fit patients who could potentially undergo courses of intensive chemotherapy and are randomized to low intensity courses	Other: Low intensity therapy; Low intensity therapy (Aza+Ven, Dac+Ven, LDARA-C+Ven)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival of patients with R/R AML depending on the use of high or low intensity therapy exposure before alloHSCT	Evaluation method: Kaplan-Meier curves and log-rank test, censored for transplantation	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probability of achieving CR in patients with R/R AML, depending on the use of high or low intensity treatment regimens	Assessment method: Chi-square test	3 months
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	Assessment method: Chi-square test	3 months
Cumulative incidence of alloHSCT in patients with R/R AML, depending on the use of high or low intensity treatment regimens	Evaluation method: cumulative frequency curves and Gray's test	2 years
Toxicity of high versus low intensity regimens	Evaluation method: Chi-square test, parametric/nonparametric tests for means Variables to be evaluated: Maximum degree and duration of neutropenia and/or thrombocytopenia;; Development of uncontrolled/life-threatening infectious complications;; Development of life-threatening hemorrhagic complications;; Development of severe organ failure.	3 months
OS over the entire duration of the study, including follow-up after alloHSCT	Evaluation method: Kaplan-Meier curves and log-rank test	2 years
RFS in patients with R/R AML when achieving remission before alloHSCT, depending on the use of high or low intensity treatment regimens	Evaluation method: Kaplan-Meier curves and log-rank test	2 years
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	Evaluation method: cumulative frequency curves and Gray's test	2 years
EFS of patients with R/R AML depending on the use of high or low intensity regimens, regardless of alloHSCT	Evaluation method: Farington-Manning test, not censored for transplantation	2 years
Statistics on discontinued participation in the protocol and premature withdrawal from the study	Assessment method: Chi-square test	2 years

Collaborators and Investigators

• Sponsor: National Research Center for Hematology, Russia
• Collaborators: St. Petersburg State Pavlov Medical University; Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: May 13, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Allogeneic Stem Cell Transplantation; Acute myeloid leukemia; Refractory AML; Relapse of AML
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Recurrence
• Other Study ID Numbers: IMPACT-AML

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Each center participating in the study includes patients and fills CRF forms separately.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No