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

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

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

Study Overview

• Status: Recruiting
• Conditions: AML; Refractory/Relapse Acute Myeloid Leukemia
• Intervention / Treatment: Drug: CAR-T cells chimeric antigen receptor T cells

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.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiangyu Zhao, M.D,Ph.D; Phone Number: 010-88325531; Email: Zhao_xy@bjmu.edu.cn
• Study Contact Backup: Name: Meng Lv, M.D., Ph.D; Phone Number: 010-88316617; Email: drlvmeng@bjmu.edu.cn

Study Locations

• China
  • Beijing, China, 100044
    • Recruiting
    • Peking University People's Hospital
    • Sub-Investigator: Meng Lv, M.D, Ph.D
    • Contact: Meng Lv, M.D,Ph.D; Phone Number: 010-88316617; Email: drlvmeng@bjmu.edu.cn
    • Principal Investigator: Xiangyu Zhao, M.D, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-70 years (inclusive), male or female.
2. 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.
3. Bone marrow blasts ≥5% by morphology.
4. Estimated life expectancy >12 weeks.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

6. Adequate organ function without ongoing supportive care, defined as:

   1. Cardiac: left ventricular ejection fraction (LVEF) ≥50%;
   2. Hepatic: ALT and AST ≤2.5 × upper limit of normal (ULN), and total bilirubin ≤2 × ULN;
   3. Renal: creatinine clearance ≥30 mL/min (calculated using the Cockcroft-Gault formula);
   4. 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:

1. Participants were diagnosed with acute promyelocytic leukemia (APL), BCR-ABL positive leukemia (chronic myeloid leukemia in acute phase), central nervous system leukemia;
2. Participants with a history of epilepsy or other central nervous system disease;
3. Participants who have previously received autologous or allogeneic CAR-T therapy;
4. Participants who have received autologous stem cell transplantation or allogeneic stem cell transplantation within 12 weeks
5. Participants who have received prior immunotherapy targeting NKG2DL;
6. Participant has clinically significant active GVHD or is receiving systemic corticosteroids for GVHD;
7. 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:

1. New York Heart Association Class III-IV heart failure;
2. History of myocardial infarction, coronary artery bypass grafting, or unstable angina within 6 months prior to Qinglin;
3. History of uncontrolled arrhythmia of significant clinical significance (as judged by the investigator), such as ventricular arrhythmia;
4. History of severe nonischemic ardiomyopathy;
5. 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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CAR-T cells chimeric antigen receptor T cells; CT0890B cells infusion

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; Other Names: Off-the-shelf allogeneic CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE) after CT0890B infusion	An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria	12 months after CT890B infusion
Dose-limiting toxicity (DLT)	The DLT is evaluated as the proportion of patients who experienced adverse events related to CT0890B that meet the criteria for DLT events after the first infusion	Up to 28 days after CAR-T cells infusion
MTD and/or dose range	Evaluate Dose limited toxicity and recommended dosage range after CT0890B infusion	Up to 28 days after CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite response (CRc)	The composite response rate (CRc) included complete response (CR), complete response with partial hematologic recovery (CRh), complete response with incomplete hematologic recovery (CRi), and morphologic leukemia-free state (MLFS). Responses were assessed in accordance with the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and the 2022 European LeukemiaNet criteria for acute myeloid leukemia (AML).	12 months after CT0890B infusion
Partial response (PR)	Partial response (PR) was defined and assessed according to the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and the 2022 European LeukemiaNet response criteria for AML.	12 months after CT0890B infusion
Rate of Subsequent Stem Cell Transplantation After CAR-T Therapy	This secondary endpoint was defined as the proportion of patients who proceeded to stem cell transplantation after CAR-T therapy during the study period.	12 months after CT0890B infusion
Duration of response (DOR)	Patients achieving CR, CRi, CRh, or MLFS were included in the duration of response (DOR) analysis set. DOR was defined as the time from the date of first documented response to the date of disease relapse or death from any cause, whichever occurred first.	12 months after CT0890B infusion
Event-free survival (EFS)	EFS was defined as the time from the date of CAR-T infusion to the earliest occurrence of treatment failure, relapse, or death from any cause. Treatment failure was defined as failure to achieve CR, CRh, CRi, MLFS, or PR at both prespecified efficacy assessments. Relapse included hematologic or extramedullary relapse after achieving CR, CRh, CRi or MLFS. For patients with treatment failure (ineffective therapy), the primary EFS analysis assigned an event time of 1 day (i.e., the time from infusion to treatment receipt). Sensitivity analyses were performed using alternative definitions of event timing, including the actual date of treatment failure, the end of treatment, or the initiation of subsequent anti-leukemia therapy.	12 months after CT0890B infusion
Overall survival (OS)	OS is defined as the time from the date of receiving the infusion to the date of death from any cause.	12 months after CT0890B infusion
Minimal Residual Disease (MRD) Negativity Rate	MRD negativity rate was assessed in participants who achieved CR, CRh, CRi or MLFS. MRD negativity was defined as <0.01% abnormal cells among CD45-positive cells as determined by multiparameter flow cytometry (MFC).	12 months after CT0890B infusion
Pharmacokinetic Endpoint - Peak expansion (Cmax)	The maximum concentration or peak value of CT0890B cells in plasma after infusion, measured by CAR copy number.	12 months after CT0890B infusion
Time to peak expansion (Tmax) of CT0890B	The time required to reach the peak expansion (maximum CAR copy number) in plasma following the infusion of CT0890B cells.	12 months after CT0890B infusion
Area under the curve (AUC) of CT0890B	The total cellular exposure in plasma after infusion, calculated based on the area under the CAR copy number-time curve.	12 months after CT0890B infusion
In vivo persistence of CT0890B	The duration for which CT0890B cells remain detectable in the plasma after infusion, monitored via CAR copy number.	Up to 12 months after CT0890B infusion

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: CARsgen Therapeutics Co., Ltd.
• Investigators: Principal Investigator: XiangYu Zhao, M.D, Ph.D, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 7, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: May 1, 2026
• First Submitted That Met QC Criteria: May 23, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 23, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: AML; Universal CAR-T; CT0890B
• Other Study ID Numbers: CT0890B-CG8001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No