CAR-T, Myeloid Malignancies
Conditions
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).
Interventions
DRUGCD33/CD123/CLL-1 CAR-T Cells
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.
Sponsors
Hebei Taihe Chunyu Biotechnology Co., Ltd
Tongji Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of adverse events | Day 28 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Duration of response (DOR) | At 3, 6, 9, 12, 18, and 24 months post-treatment follow up |
Other
| Measure | Time frame | Description |
|---|---|---|
| Kinetics of CAR-T cells | 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. |
Countries
China
Contacts
Primary ContactJia Wei
Outcome results
None listed