## Protocol Section
### Identification Module
**NCT ID:** NCT06418776

**Brief Title:** 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

#### Organization Study ID Info
**ID:** IMPACT-AML
#### Organization
**Class:** NETWORK
**Full Name:** National Research Center for Hematology, Russia
### Status Module
#### Completion Date
**Date:** 2029-05

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2027-04

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-04-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-09
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** St. Petersburg State Pavlov Medical University

**Class:** OTHER

**Name:** Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

#### Lead Sponsor

**Class:** NETWORK

**Name:** National Research Center for Hematology, Russia

#### Responsible Party

**Investigator Affiliation:** National Research Center for Hematology, Russia

**Investigator Full Name:** Elena N.Parovichnikova

**Investigator Title:** General director of National Medical Research Center for Hematology

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**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).

### Conditions Module

**Conditions:**

- Refractory Acute Myeloid Leukemia

- Early Relapses of Acute Myeloid Leukemia

**Keywords:**

- Acute myeloid leukemia

- Relapse of AML

- Refractory AML

- Allogeneic Stem Cell Transplantation

### Design Module

#### Design Info

**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.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 198

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Other: Intensive therapy

**Label:** Intensive arm

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

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

**Intervention Names:**

- Other: Low intensity therapy

**Label:** Low-intensive arm

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intensive arm

**Description:** Intensive chemotherapy courses (MEC, FLAG, FLAG-Ida, FLAG-Mito)

**Name:** Intensive therapy

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- Low-intensive arm

**Description:** Low intensity therapy (Aza+Ven, Dac+Ven, LDARA-C+Ven)

**Name:** Low intensity therapy

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Evaluation method: Kaplan-Meier curves and log-rank test, censored for transplantation

**Measure:** Event-free survival of patients with R/R AML depending on the use of high or low intensity therapy exposure before alloHSCT

**Time Frame:** 2 years

#### Secondary Outcomes

**Description:** Assessment method: Chi-square test

**Measure:** Probability of achieving CR in patients with R/R AML, depending on the use of high or low intensity treatment regimens

**Time Frame:** 3 months

**Description:** Assessment method: Chi-square test

**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

**Time Frame:** 3 months

**Description:** Evaluation method: cumulative frequency curves and Gray's test

**Measure:** Cumulative incidence of alloHSCT in patients with R/R AML, depending on the use of high or low intensity treatment regimens

**Time Frame:** 2 years

**Description:** 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.

**Measure:** Toxicity of high versus low intensity regimens

**Time Frame:** 3 months

**Description:** Evaluation method: Kaplan-Meier curves and log-rank test

**Measure:** OS over the entire duration of the study, including follow-up after alloHSCT

**Time Frame:** 2 years

**Description:** Evaluation method: Kaplan-Meier curves and log-rank test

**Measure:** RFS in patients with R/R AML when achieving remission before alloHSCT, depending on the use of high or low intensity treatment regimens

**Time Frame:** 2 years

**Description:** Evaluation method: cumulative frequency curves and Gray's test

**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

**Time Frame:** 2 years

**Description:** Evaluation method: Farington-Manning test, not censored for transplantation

**Measure:** EFS of patients with R/R AML depending on the use of high or low intensity regimens, regardless of alloHSCT

**Time Frame:** 2 years

**Description:** Assessment method: Chi-square test

**Measure:** Statistics on discontinued participation in the protocol and premature withdrawal from the study

**Time Frame:** 2 years

### Eligibility Module

**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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** kashlakova.a.i@gmail.com

**Name:** Anastasia Kashlakova, MD

**Phone:** +79629087553

**Role:** CONTACT

**Contact 2:**

**Email:** parovichnikova.e@blood.ru

**Name:** Elena Parovichnikova, MD

**Phone:** +74956122123

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Moscow

**Contacts:**

***Contact 1:***

- **Email:** director@blood.ru

- **Name:** Elena Parovichnikova, MD

- **Phone:** +74956122361

- **Role:** CONTACT

***Contact 2:***

- **Email:** kashlakova.a@blood.ru

- **Name:** Anastasia Kashlakova, MD

- **Phone:** +74956124592

- **Role:** CONTACT

**Country:** Russian Federation

**Facility:** National Research Center for Hematology

**Status:** RECRUITING

**Zip:** 125167

### IPD Sharing Statement Module

**Description:** Each center participating in the study includes patients and fills CRF forms separately.

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M10955

- Name: Leukemia, Myeloid

- Relevance: HIGH

- As Found: Myeloid Leukemia

- ID: M18127

- Name: Leukemia, Myeloid, Acute

- Relevance: HIGH

- As Found: Acute Myeloid Leukemia

- ID: M14850

- Name: Recurrence

- Relevance: HIGH

- As Found: Relapse

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T3995

- Name: Myeloid Leukemia

- Relevance: HIGH

- As Found: Myeloid Leukemia

- ID: T182

- Name: Acute Myeloid Leukemia

- Relevance: HIGH

- As Found: Acute Myeloid Leukemia

- ID: T188

- Name: Acute Non Lymphoblastic Leukemia

- Relevance: HIGH

- As Found: Acute Myeloid Leukemia

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007938

- Term: Leukemia

- ID: D000007951

- Term: Leukemia, Myeloid

- ID: D000015470

- Term: Leukemia, Myeloid, Acute

- ID: D000012008

- Term: Recurrence

### Misc Info Module

- Version Holder: 2024-05-31
