Exploratory Clinical Study on the Safety and Efficacy of CAR-T Cell Therapy in the Treatment of Relapsed/Refractory Myeloid Malignancies

Phase 1

Not yet recruiting

• Conditions: Myeloid Malignancies; CAR-T
• Interventions: Drug: CD33/CD123/CLL-1 CAR-T Cells

• Registration Number: NCT06917105
• Lead Sponsor: Tongji Hospital

Brief Summary

This is an open-label, single-arm, exploratory clinical trial utilizing a "3+3" dose escalation followed by dose expansion to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of CD33/CD123/CLL-1 CAR-T cell therapy in patients with relapsed/refractory myeloid malignancies.

Part A: Dose Escalation Phase. Follows a "3+3" dose escalation design with four predefined dose cohorts: 0.2×10⁶, 0.5×10⁶, 1×10⁶, and 2×10⁶ CAR-positive cells/kg.Anticipated enrollment: 12-24 subjects.Primary objectives: Assess safety, tolerability, and determine MTD.Dose-limiting toxicity (DLT) observation period: 28 days post-infusion.

Part B: Dose Expansion Phase.Enrolls 21 additional subjects to receive CAR-T cell infusion at the recommended Phase 2 dose (RP2D) established in Part A.Primary objective: Further evaluate therapeutic efficacy.

Overall Study Objectives:Safety profile of CD33/CD123/CLL-1 CAR-T therapy.Efficacy endpoints (e.g., response rates, survival outcomes).Pharmacokinetic characterization of CAR-T cells (expansion/persistence).

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study Start: 2025-04-01
• Study First Submitted: 2025-04-01
• Study First Submitted QC: 2025-04-01
• Last Update Submitted: 2025-04-01
• Study First Posted: 2025-04-08
• Last Update Posted: 2025-04-08
• Primary Completion: 2027-04-30
• Study Completion: 2029-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Informed Consent: Willing and able to provide written informed consent, with commitment to comply with scheduled visits, study treatment, laboratory tests, and other trial procedures.

Age: ≥18 years, regardless of gender.

Diagnosis: Pathologically confirmed myeloid malignancy (including but not limited to AML or MDS) meeting relapsed/refractory criteria:

Relapsed Disease: Reappearance of leukemic cells in peripheral blood, bone marrow blasts >5%, or extramedullary relapse after achieving CR/CRi with ≥2 lines of salvage therapy.

Refractory Disease: Failure to achieve CR/CRi after ≥2 cycles of standard intensive chemotherapy.

Antigen Expression: Tumor cell positivity for CD33, CD123, and/or CLL-1 confirmed by immunohistochemistry (IHC) or flow cytometry.

Life Expectancy: ≥3 months from the date of informed consent signing. Hematologic Criteria: Hemoglobin ≥70 g/L (transfusion permitted).

Organ Function:

Renal: Serum creatinine ≤1.5×ULN. Cardiac: Left ventricular ejection fraction (LVEF) ≥50%. Pulmonary: Oxygen saturation >90% on room air. Hepatic: Total bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score 0-2.

Exclusion Criteria

• Cardiac Dysfunction: Severe cardiac insufficiency with left ventricular ejection fraction (LVEF) <50%.

Pulmonary Disease: History of severe pulmonary dysfunction (e.g., chronic respiratory failure, interstitial lung disease, or pulmonary hypertension requiring oxygen therapy).

Concurrent Malignancy: Active/progressive malignancy other than myeloid neoplasms (exceptions: adequately treated non-melanoma skin cancer or carcinoma in situ).

Uncontrolled Infection: Active severe infection requiring systemic antimicrobial therapy (antibacterial, antiviral, or antifungal) without clinical resolution.

Immune Disorders:

Severe autoimmune disease requiring immunosuppressive therapy within 6 months. Primary immunodeficiency disorders (e.g., common variable immunodeficiency, severe combined immunodeficiency).

Viral Infections:

Active hepatitis B (HBV-DNA ≥2000 IU/mL) or hepatitis C (HCV-RNA positive). HIV infection, AIDS, or untreated syphilis (confirmed by serological testing). Hypersensitivity: History of severe allergic reaction (Grade ≥3) to biological products, including antibiotics.

Transplant Complications: Allogeneic hematopoietic stem cell transplant recipients with:

Acute graft-versus-host disease (GvHD) ≥ Grade II within 3 months. Ongoing immunosuppressive therapy for GvHD within 4 weeks.

General Exclusion:

Any physical, psychiatric, or laboratory abnormality that may:

Significantly increase study risk (e.g., uncontrolled diabetes, NYHA Class III/IV heart failure).

Compromise protocol compliance or data interpretation. Investigator-determined unsuitability for trial participation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T Cells infusion（ CD33/CD123/CLL-1 CAR-T）	CD33/CD123/CLL-1 CAR-T Cells	-

Primary Outcome Measures

Name	Time	Method
The incidence of adverse events	Day 28

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
Complete response rate (CRR)	At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
Duration of response (DOR)	At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
Progression free survival (PFS)	At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
Overall survival (OS)	At 3, 6, 9, 12, 18, and 24 months post-treatment follow up

Trial Locations

Locations (1)

Tongji Hospital affiliated to Tongji Medical College of Huazhong University; 🇨🇳 WuHan, Hubei, China