## Protocol Section
### Identification Module
**NCT ID:** NCT06420063

**Acronym:** BAH244

**Brief Title:** Sequential CAR-T Cells Targeting CD33/CD123 in Patients With Acute Myelocytic Leukemia AML

**Official Title:** Sequential CAR-T Cell Infusion Targeting CD33 and CD123 for Refractory/Relapsed Acute Myeloid Leukaemia

#### Organization Study ID Info
**ID:** ESBI202495
#### Organization
**Class:** OTHER
**Full Name:** Essen Biotech
### Status Module
#### Completion Date
**Date:** 2026-12-28

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-12-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-10-10

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Essen Biotech

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This is an open, single-arm, clinical study to evaluate the efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) targeting CD33 or CD123 or both sequentially in the treatment of Acute Myelocytic Leukemia.

**Detailed Description:** Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may have the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of CAR-T targeting CD33/CD123 in patients with Acute Myelocytic Leukemia. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.

The purpose of this clinical trial is to assess the feasibility, safety, and efficacy of multiple CAR T-cell therapy which combines CAR T cells against AML Cells with CAR T cells targeting CD123 or CD33 in patients with relapsed and refractory AML. The study also aims to learn more about the function of CAR T cells and their persistence in AML patients.

### Conditions Module

**Conditions:**

- AML

- Acute Myeloid Leukemia

- AML, Adult Recurrent

- AML, Adult

**Keywords:**

- aml

- cd33

- cd123

- CAR-T

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Patients enrolled in this clinical trial will receive a carefully designed treatment regimen. Before the infusion of CD33 and CD123 CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to create an optimal environment for CAR-T cell therapy to effectively target and eliminate malignant B cells. Following chemotherapy, participants will receive the infusion of CD33 and CD123 CAR-T cells.

##### Masking Info

**Masking:** NONE

**Masking Description:** Open-label clinical trials are a category of clinical research where the masking is minimal or nonexistent. In such trials, both the participants and the researchers are fully aware of the treatment assignments, which means participants know the treatment they are receiving, and researchers are aware of each participant's treatment group.

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 85

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients will be administered fludarabine phosphate intravenously (IV) over a 30-minute period on days -4 to -2. Additionally, cyclophosphamide will be administered intravenously (IV) over 60 minutes on day -2. Subsequently, patients will receive CD33/123 CAR T cells intravenously (IV) over a duration of 10-20 minutes on day 0. Patients who exhibit positive responses to the initial dose of CD33/123 CAR T cells, do not experience unacceptable side effects, and have a sufficient quantity of cells available may be eligible to receive 2 or 3 additional doses of CD33/CD123 CAR T cells.

**Intervention Names:**

- Biological: CD123/CD33 CART

**Label:** Treatment (CD33/CD123 CAR T cells, chemotherapy)

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Treatment (CD33/CD123 CAR T cells, chemotherapy)

**Description:** The intervention in this clinical trial involves a novel approach using CD22/123-Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies.

Treatment Regimen:

Patients in the trial will undergo the following regimen:

Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy.

Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2.

CD33/123-Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, CD33/123-CAR T cells, over 10-20 minutes on day 0.

Additional Doses: Eligible patients responding well to the initial CD33/123 CAR-T cell infusion without unacceptable side effects and sufficient CAR T cell availability may receive 2 or 3 additional doses.

**Name:** CD123/CD33 CART

**Other Names:**

- EB-BH2025

**Type:** BIOLOGICAL

### Outcomes Module

#### Primary Outcomes

**Description:** Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at three dose levels until the maximum tolerated dose (MTD) is determined.

**Measure:** Incidence and severity of dose-limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD5/CD7 chimeric antigen receptor (CAR) T cells

**Time Frame:** 28 days

#### Secondary Outcomes

**Description:** satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA)

**Measure:** Rate of successful manufacture and expansion of the CD33/123 chimeric antigen receptor (CAR) T cells

**Time Frame:** 10-14 days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Subjects with acute myeloid leukemia who voluntarily signed informed consent and met the following criteria:
* Age older than 6 months.
* Confirmed expression of CLL-1, CD123 and/or CD33 in blast AML by immuno-histochemical staining or flow cytometry.
* Karnofsky performance status (KPS) score is higher than 80 and life expectancy \> 3 months.
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤ 2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL.
* Hgb≥80g/L.
* No cell separation contraindications.
* Abilities to understand and the willingness to provide written informed consent.

Exclusion Criteria:

* Severe illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
* Active bacterial, fungal or viral infection not controlled by adequate treatment.
* Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
* Pregnant or nursing women may not participate.
* Use of glucocorticoid for systemic therapy within one week prior to entering the trial.
* Patients, in the opinion of investigators, may not be able to comply with the study.

**Maximum Age:** 90 Years

**Minimum Age:** 6 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ceo@essen-biotech.com

**Name:** JAMAL ALKHAYER

**Phone:** +97333799773

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Shanghai

**Country:** China

**Facility:** District one hospital

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## 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: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M14850

- Name: Recurrence

- Relevance: LOW

- As Found: Unknown

- 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 - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M6727

- Name: Cyclophosphamide

- Relevance: LOW

- As Found: Unknown

- ID: M283230

- Name: Fludarabine

- Relevance: LOW

- As Found: Unknown

- ID: M225513

- Name: Fludarabine phosphate

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
