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

NCT06917105 | Not Yet Recruiting Phase 1

• 1 other identifier: TJ-IRB202503062
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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).

Conditions

Myeloid Malignancies; CAR-T

Outcome Measures

Primary Outcomes (1)

• The incidence of adverse events

  Day 28

Secondary Outcomes (5)

• 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

Other Outcomes (1)

• Kinetics of CAR-T cells

  At 3, 6, 9, 12, 18, and 24 months post-treatment follow up

Study Arms (1)

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

EXPERIMENTAL

Drug: CD33/CD123/CLL-1 CAR-T Cells

Interventions

CD33/CD123/CLL-1 CAR-T Cells DRUG

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.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Tongji Hospital: lead
• Hebei Taihe Chunyu Biotechnology Co., Ltd: collaborator

Study Sites (1)

Tongji Hospital affiliated to Tongji Medical College of Huazhong University

Wuhan, Hubei, 430030, China

Location

Central Study Contacts

Jia Wei

CONTACT

+86 13986102084; jiawei@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 8, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2029
• Last Updated: April 8, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)