Allogeneic CAR-T(CT0890B) in NKG2DL+ R/R AML

Official title

A Phase I Study to Evaluate the Safety and Efficacy of Allogeneic CAR-T Cells (CT0890B) in Patients With NKG2DL-Positive Relapsed/Refractory Acute Myeloid Leukemia

Overview

A Clinical Study to Investigate the Safety and Efficacy of CT0890B in Patients with Relapsed/Refractory Acute Myeloid Leukemia.

Detailed description

This is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, efficacy, and cellular pharmacokinetics of CT0890B in patients with relapsed or refractory acute myeloid leukemia. It is planned to enroll 12\~27 participants in this trial.

Interventions

• Drug CAR-T cells chimeric antigen receptor T cells
  Conditioning regimen: Days -9 to -3: Venetoclax administered with a target dose of 200 mg/day. Days -5 to -4: Cytarabine administered at 500 mg/m²/day. Days -5 to -3: Cyclophosphamide at 300 mg/m²/day plus Fludarabine at 30 mg/m²/day. Day 0: Infusion of CT0890B CAR-T cells at one of four dose levels using an i3+3 Dose-Escalation Design: 1.5 × 10⁸ total cells, 3.0 × 10⁸ total cells, 4.5 × 10⁸ total cells, 6.0 × 10⁸ total cells

Primary outcome measures

• Adverse Events (AE) after CT0890B infusion [Time frame: 12 months after CT890B infusion]
• Dose-limiting toxicity (DLT) [Time frame: Up to 28 days after CAR-T cells infusion]
• MTD and/or dose range [Time frame: Up to 28 days after CAR-T cells infusion]

Secondary outcome measures (11)

• Composite response (CRc) [Time frame: 12 months after CT0890B infusion]
• Partial response (PR) [Time frame: 12 months after CT0890B infusion]
• Rate of Subsequent Stem Cell Transplantation After CAR-T Therapy [Time frame: 12 months after CT0890B infusion]
• Duration of response (DOR) [Time frame: 12 months after CT0890B infusion]
• Event-free survival (EFS) [Time frame: 12 months after CT0890B infusion]
• Overall survival (OS) [Time frame: 12 months after CT0890B infusion]
• Minimal Residual Disease (MRD) Negativity Rate [Time frame: 12 months after CT0890B infusion]
• Pharmacokinetic Endpoint - Peak expansion (Cmax) [Time frame: 12 months after CT0890B infusion]
• Time to peak expansion (Tmax) of CT0890B [Time frame: 12 months after CT0890B infusion]
• Area under the curve (AUC) of CT0890B [Time frame: 12 months after CT0890B infusion]
• In vivo persistence of CT0890B [Time frame: Up to 12 months after CT0890B infusion]

Eligibility criteria

Inclusion criteria

• Age 18-70 years (inclusive), male or female.
• Relapsed or refractory acute myeloid leukemia (R/R AML) diagnosed according to the 2022 World Health Organization classification or ELN criteria, with confirmed NKG2D ligand-positive disease.
• Bone marrow blasts ≥5% by morphology.
• Estimated life expectancy >12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate organ function without ongoing supportive care, defined as:

• Cardiac: left ventricular ejection fraction (LVEF) ≥50%;
• Hepatic: ALT and AST ≤2.5 × upper limit of normal (ULN), and total bilirubin ≤2 × ULN;
• Renal: creatinine clearance ≥30 mL/min (calculated using the Cockcroft-Gault formula);
• Coagulation: activated partial thromboplastin time (APTT) ≤1.5 × ULN and prothrombin time (PT) ≤1.5 × ULN.

c) Renal: creatinine clearance ≥30 mL/min (calculated using the Cockcroft-Gault formula); d) Coagulation: activated partial thromboplastin time (APTT) ≤1.5 × ULN and prothrombin time (PT) ≤1.5 × ULN.

Exclusion criteria

• Participants were diagnosed with acute promyelocytic leukemia (APL), BCR-ABL positive leukemia (chronic myeloid leukemia in acute phase), central nervous system leukemia;
• Participants with a history of epilepsy or other central nervous system disease;
• Participants who have previously received autologous or allogeneic CAR-T therapy;
• Participants who have received autologous stem cell transplantation or allogeneic stem cell transplantation within 12 weeks
• Participants who have received prior immunotherapy targeting NKG2DL;
• Participant has clinically significant active GVHD or is receiving systemic corticosteroids for GVHD;
• Participant has any of the following at screening:

1)Active, uncontrolled systemic infection or requiring intravenous anti-infective agents 2)Any of the following cardiac conditions, including:

• New York Heart Association Class III-IV heart failure;
• History of myocardial infarction, coronary artery bypass grafting, or unstable angina within 6 months prior to Qinglin;
• History of uncontrolled arrhythmia of significant clinical significance (as judged by the investigator), such as ventricular arrhythmia;
• History of severe nonischemic ardiomyopathy;
• Other cardiac disease that the investigatorbelieve could jeopardize the participant 's well-being or compromise participation in this clinical trial; 3) Active bleeding of clinical significance as judged by the investigator; 4)Requiring supplemental oxygen to maintain oxygen saturation> 92%; 5)Patients with severe chronic obstructive pulmonary disease (COPD) or other lung diseases that cannot tolerate CAR-T treatment as judged by the investigator;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University People's Hospital — Beijing

Identifiers

NCT: NCT07617285 · CT0890B-CG8001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗