exploratory clinical study on the safety and efficacy of car-t cell therapy in the treatment of relapsed/refractory myeloid malignancies

Conditions: Myeloid Malignancies; CAR-T

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).


Eligibility criteria:
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.