AML, Refractory/Relapse Acute Myeloid Leukemia
Conditions
Keywords
CT0890B, Universal CAR-T, AML
Brief summary
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
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
Sponsors
Peking University People's Hospital
CARsgen Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single Group Assignment of CAR-T
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AE) after CT0890B infusion | 12 months after CT890B infusion | An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria |
| Dose-limiting toxicity (DLT) | Up to 28 days after CAR-T cells infusion | 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 |
| MTD and/or dose range | Up to 28 days after CAR-T cells infusion | Evaluate Dose limited toxicity and recommended dosage range after CT0890B infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite response (CRc) | 12 months after CT0890B infusion | 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). |
| Partial response (PR) | 12 months after CT0890B infusion | 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. |
| Rate of Subsequent Stem Cell Transplantation After CAR-T Therapy | 12 months after CT0890B infusion | This secondary endpoint was defined as the proportion of patients who proceeded to stem cell transplantation after CAR-T therapy during the study period. |
| Duration of response (DOR) | 12 months after CT0890B infusion | 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. |
| Event-free survival (EFS) | 12 months after CT0890B infusion | 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. |
| Overall survival (OS) | 12 months after CT0890B infusion | OS is defined as the time from the date of receiving the infusion to the date of death from any cause. |
| Minimal Residual Disease (MRD) Negativity Rate | 12 months after CT0890B infusion | 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). |
| Pharmacokinetic Endpoint - Peak expansion (Cmax) | 12 months after CT0890B infusion | The maximum concentration or peak value of CT0890B cells in plasma after infusion, measured by CAR copy number. |
| Time to peak expansion (Tmax) of CT0890B | 12 months after CT0890B infusion | The time required to reach the peak expansion (maximum CAR copy number) in plasma following the infusion of CT0890B cells. |
| Area under the curve (AUC) of CT0890B | 12 months after CT0890B infusion | The total cellular exposure in plasma after infusion, calculated based on the area under the CAR copy number-time curve. |
| In vivo persistence of CT0890B | Up to 12 months after CT0890B infusion | The duration for which CT0890B cells remain detectable in the plasma after infusion, monitored via CAR copy number. |
Countries
China
Contacts
CONTACTXiangyu Zhao, M.D,Ph.D
CONTACTMeng Lv, M.D., Ph.D
PRINCIPAL_INVESTIGATORXiangYu Zhao, M.D, Ph.D
Peking University People's Hospital
Outcome results
None listed