## Protocol Section
### Identification Module
**NCT ID:** NCT06429098

**Brief Title:** Study of A Venetoclax-based, Anthracycline-free Regimen in Newly Diagnosed CBFβ::MYH11(+) AML

**Official Title:** Study of A Venetoclax-based, Anthracycline-free Regimen in Patients With Newly Diagnosed CBFβ::MYH11-positive Acute Myeloid Leukemia

#### Organization Study ID Info
**ID:** 2023371
#### Organization
**Class:** OTHER
**Full Name:** The First Affiliated Hospital of Soochow University
### Status Module
#### Completion Date
**Date:** 2027-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2027-06-30

**Type:** ESTIMATED

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

**Type:** ACTUAL

**Status Verified Date:** 2023-12

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** The First Affiliated Hospital of Soochow University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** This investigator-initiated, single-arm, phase II trial is aimed to evaluate the efficacy and safety of a venetoclax-based, anthracycline-free regimen in patients with newly diagnosed CBFβ::MYH11-positive acute myeloid leukemia.

**Detailed Description:** Primary Objectives:

To determine the CR (complete remission) / CRi (complete remission with incomplete blood count recovery) rate of 2 cycles of VEN/HMA in patients with newly diagnosed (ND) CBFβ::MYH11-positive acute myeloid leukemia(AML).

Secondary Objectives:

1. To determine the overall response rate (ORR) of 2 cycles of VEN/HMA in patients with ND CBFβ::MYH11-positive AML.
2. To determine the safety of the combination regimen.
3. To study the trajectories of molecular measurable residual disease (MRD) during the therapy.
4. To evaluate the impact of baseline genomic alterations on response and survival of the combination regimen.
5. To assess the duration of response, overall survival (OS) and event free survival (EFS) of patients.

OUTLINE:

INDUCTION:

Patients with newly diagnosed CBFβ::MYH11(+) AML receive 2 cycles of VEN/HMA as induction therapy. Venetoclax orally (PO) once daily (QD) on days 1-28, azacitidine subcutaneously (SC) on days 1-7 or decitabine intravenously (IV) over 30-60 minutes on days 1-5.

CONSOLIDATION:

Patient fitness will be reassessed according to the Ferrara criteria if CR or CRi is achieved after 2 cycles of VEN/HMA. Fit patients will receive four cycles of consolidation therapy with high-dose cytarabine (2g/m2 every 12 hours, on days 1-3) combined with venetoclax (on days 1-7). Unfit patients will continue to receive VEN/HMA until disease progression.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

### Conditions Module

**Conditions:**

- Acute Myeloid Leukemia

**Keywords:**

- venetoclax

- acute myeloid leukemia

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** INDUCTION: Patients receive 2 cycles of VEN/HMA as induction therapy. Venetoclax orally (PO) once daily (QD) on days 1-28, azacitidine subcutaneously (SC) on days 1-7 or decitabine intravenously (IV) over 30-60 minutes on days 1-5.

CONSOLIDATION: Fit patients will receive four cycles of consolidation therapy with high-dose cytarabine (2g/m2 every 12 hours, on days 1-3) combined with venetoclax (on days 1-7). Unfit patients will continue to receive VEN/HMA until disease progression.

**Intervention Names:**

- Drug: Venetoclax

- Drug: azacitidine

- Drug: decitabine

- Drug: Cytarabine

**Label:** Venetoclax, Azacitidine/Decitabine/, Cytarabine

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Venetoclax, Azacitidine/Decitabine/, Cytarabine

**Description:** Given PO, once daily. Treatment in cycle 1, the dose is 100 mg on day 1, then ramp up to 400mg. In all subsequent cycles, the dose of venetoclax is initiated at 400 mg daily.

**Name:** Venetoclax

**Other Names:**

- ABT-199

- ABT199

- Venclexta

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Venetoclax, Azacitidine/Decitabine/, Cytarabine

**Description:** Given SC

**Name:** azacitidine

**Other Names:**

- 5 AZC

- 5-AZC

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Venetoclax, Azacitidine/Decitabine/, Cytarabine

**Description:** Given IV

**Name:** decitabine

**Other Names:**

- Dacogen

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Venetoclax, Azacitidine/Decitabine/, Cytarabine

**Description:** Given IV

**Name:** Cytarabine

**Other Names:**

- 1-.beta.-Cytosine arabinoside

- Ara-C

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** CR/CRi rate will be determined.

**Measure:** composite complete remission rate

**Time Frame:** after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days).

#### Secondary Outcomes

**Description:** ORR will be determined.

**Measure:** Overall response rate (ORR)

**Time Frame:** after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days).

**Description:** Safety profile based on NCI CTCAE version 5.0 will be determined.

**Measure:** Incidence of adverse events

**Time Frame:** From the start of treatment until death or last follow-up, assessed for up to 3 years.

**Description:** MRD will be assessed by real-time qRCR.

**Measure:** measurable residual disease (MRD) negativity

**Time Frame:** From the start of treatment until death or last follow-up, assessed for up to 3 years.

**Description:** The impact of concurrent gene mutations ( analysis via an 81-gene institutional next-generation sequencing platform) on response and the survival of the combination regimen will be assessed.

**Measure:** Impact of concurrent gene mutations

**Time Frame:** Baseline

**Description:** OS will be assessed.

**Measure:** Overall survival (OS)

**Time Frame:** From the start of treatment until death or last follow-up, assessed for up to 3 years.

**Description:** EFS will be assessed.

**Measure:** Event-free survival (EFS)

**Time Frame:** up to 3 years.

**Description:** DOR will be assessed.

**Measure:** Duration of response (DOR)

**Time Frame:** up to 3 years.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Adults ≥ 18 years.
2. Newly diagnosed CBFβ::MYH11(+) AML.
3. Performance status 0-3 on the Eastern Cooperative Oncology Group (ECOG) Scale.
4. Subject must voluntarily sign and date an informed consent, prior to the initiation of any screening or study-specific procedures.

Ferrara's criteria are used to determine whether a patient is unfit, and a patient is deemed unfit if at least one of the following criteria is met:

1. Age\>75 years.
2. There are serious underlying heart, lung, kidney, liver complications.
3. There are active infections that do not respond to anti-infective therapy.
4. There is cognitive impairment.
5. Other comorbidities that the doctor determines are not suitable for intensive chemotherapy.

Exclusion Criteria:

1. Subject has received treatment with a hypomethylating agent and/or other chemotherapeutic agents either conventional or experimental or targeted drug therapy for AML (except oral hydroxyurea and/or leukocytometry to reduce white blood cell count).
2. Pregnant or lactating women.
3. To the knowledge of the subject and investigator, subject may not be able to complete all study visits or procedures required by the study protocol, including follow-up visits, and/or be unable to comply with the required study procedures.
4. Other conditions deemed unsuitable for participation in this study by the investigator.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** wangying77@suda.edu.cn

**Name:** Ying Wang

**Phone:** 008613656214782

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Suzhou

**Contacts:**

***Contact 1:***

- **Name:** Zhou-lin Lu

- **Phone:** 008613914086271

- **Role:** CONTACT

**Country:** China

**Facility:** Ethical Committee of the First Affiliated Hospital of Soochow University

**State:** Jiangsu

**Status:** RECRUITING

**Zip:** 215000

**Location 2:**

**City:** Suzhou

**Contacts:**

***Contact 1:***

- **Email:** wangying77@suda.edu.cn

- **Name:** Ying Wang

- **Phone:** 008613656214782

- **Role:** CONTACT

**Country:** China

**Facility:** The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

**State:** Jiangsu

**Status:** RECRUITING

**Zip:** 215000

#### Overall Officials

**Official 1:**

**Affiliation:** The First Affiliated Hospital of Soochow University

**Name:** Ying Wang

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000006402

- Term: Hematologic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- 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: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- 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

### Intervention Browse Module - Ancestors

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000004791

- Term: Enzyme Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M6766

- Name: Cytarabine

- Relevance: HIGH

- As Found: Multi-

- ID: M249656

- Name: Venetoclax

- Relevance: HIGH

- As Found: Hepatocellular Carcinoma

- ID: M4673

- Name: Azacitidine

- Relevance: HIGH

- As Found: Frequency

- ID: M1697

- Name: Decitabine

- Relevance: HIGH

- As Found: ?

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000003561

- Term: Cytarabine

- ID: D000001374

- Term: Azacitidine

- ID: D000077209

- Term: Decitabine

- ID: C000579720

- Term: Venetoclax

### Misc Info Module

- Version Holder: 2024-05-31
