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

Refractory Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06418776
• Other study ID #: IMPACT-AML
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2024
• Est. completion date: May 2029

Study information

• Verified date: May 2024
• Source: National Research Center for Hematology, Russia
• Contact: Anastasia Kashlakova, MD
• Phone: +79629087553
• Email: kashlakova.a.i[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 198
• Est. completion date: May 2029
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Recurrence
• Refractory Acute Myeloid Leukemia

Intervention

Other:
• Intensive therapy
Intensive chemotherapy courses (MEC, FLAG, FLAG-Ida, FLAG-Mito)
• Low intensity therapy
Low intensity therapy (Aza+Ven, Dac+Ven, LDARA-C+Ven)

Locations

Country	Name	City	State
Russian Federation	National Research Center for Hematology	Moscow

Sponsors (3)

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

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	OS over the entire duration of the study, including follow-up after alloHSCT	Evaluation method: Kaplan-Meier curves and log-rank test	2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Statistics on discontinued participation in the protocol and premature withdrawal from the study	Assessment method: Chi-square test	2 years