Exploratory Clinical Study on the Safety and Efficacy of CAR-T Cell Therapy in the Treatment of Relapsed/Refractory Myeloid Malignancies
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).
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Jia Wei
- Phone Number: +86 13986102084
- Email: jiawei@tjh.tjmu.edu.cn
Study Locations
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Hubei
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WuHan, Hubei, China, 430030
- Tongji Hospital affiliated to Tongji Medical College of Huazhong University
-
Contact:
- Jia Wei
- Phone Number: +8613986102084
- Email: jiawei@tjh.tjmu.edu.cn
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: CAR-T Cells infusion（ CD33/CD123/CLL-1 CAR-T）
|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
The incidence of adverse events
Time Frame: Day 28
|
Day 28
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Objective response rate (ORR)
Time Frame: At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
|
Complete response rate (CRR)
Time Frame: At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
|
Duration of response (DOR)
Time Frame: At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
|
Progression free survival (PFS)
Time Frame: At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
|
Overall survival (OS)
Time Frame: At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Kinetics of CAR-T cells
Time Frame: At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
Use flow cytometry or Q-PCR to monitor the kinetics of CAR-T cells.
|
At 3, 6, 9, 12, 18, and 24 months post-treatment follow up
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TJ-IRB202503062
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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