Relapsed/Refractory Acute Myeloid Leukemia(AML)
Conditions
Keywords
CT1390B
Brief summary
A Clinical Study to Investigate the Safety and Efficacy of CT1390B 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 CT1390B in patients with relapsed or refractory acute myeloid leukemia. It is planned to enroll 9\ 18 participants in this trial
Interventions
CT1390B cells infusion
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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 definitively diagnosed as CLL-1 positive according to the WHO 2022 classification 3. Bone marrow blast percentage ≥5% by morphology 4. Estimated survival \> 12 weeks 5. ECOG score 0-2 6. Participants should meet the following test results (no ongoing supportive care) 1. Left ventricular ejection fraction (LVEF) \> 50% 2. ALT≤ 2.5 × ULN, AST ≤ 2.5 × ULN, total bilirubin ≤ 2 × ULN; ALT≤ 5 × ULN, AST ≤ 5 × ULN, total bilirubin ≤ 3 × ULN, if the liver is involved 3. Endogenous creatinine clearance ≥ 30 mL/min (creatinine clearance calculated using the Cockcroft-Gault formula) 4. 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), active 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 CLL-1 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 Lymphodepleting Chemotherapy; 3. History of uncontrolled arrhythmia of significant clinical significance (as judged by the investigator), such as ventricular arrhythmia; 4. History of severe non-ischemic cardiomyopathy; 5. Other cardiac disease that the investigator believe 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 8. Has HIV, syphilis infection, active hepatitis B virus infection (HBsAg positive and HBV-DNA above the detection limit), or active hepatitis C virus infection (HCV antibody and HCV-DNA positive)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AE) after CT1390B infusion | 12 months after CT1390B 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 CT1390B 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 CT1390B infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR), complete response with partial hematologic recovery (CRh)，and complete response with incomplete hematologic recovery (CRi) | 12 months after CT1390B infusion | Performed according to the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and ELN 2022 Criteria for AML defined as achieving CR,CRh and CRi |
| Morphologic leukemia-free status (MLFS) and partial response (PR). | 12 months after CT1390B infusion | Performed according to the Technical Guidelines for Clinical Development of New Drugs for Acute Myeloid Leukemia and ELN 2022 Criteria for AML defined of Achieve MLFS and PR |
| Proportion of patients undergoing stem cell transplantation following CAR-T therapy. | 12 months after CT1390B infusion | — |
| Duration of response (DOR) | 12 months after CT1390B infusion | Participants achieving CR/CRi/CRh will be included in the analysis set for DOR. DOR is defined as the time from the date of confirmed response until the date of disease relapse or death from any cause, whichever occurs first |
| Event-free survival (EFS) | 12 months after CT1390B infusion | Defined as the time from the date of receiving the infusion to the date of treatment failure (failure to achieve CR/CRh/CRi/MLFS/PR after both efficacy assessments), or relapse (hematologic relapse or extramedullary relapse after CR/CRh/CRi), or death from any cause, whichever occurs first. When an EFS event was "Ineffective Therapy", the primary analysis of EFS was performed on a 1-day basis (ie, time to treatment received as the event). For a more comprehensive assessment, sensitivity analyses could be performed using the actual date of treatment failure, end of treatment, or start of next-line anti-leukemia therapy as the end of EFS for treatment failure, respectively |
| Overall survival (OS) | 12 months after CT1390B infusion | Defined as the time from the date of receiving the infusion to the date of death from any cause |
| Minimal Residual Disease (MRD) Negative Rate | 12 months after CT1390B infusion | tested in all participants who achieved CR/CRh/CRi. MRD negativity was defined as abnormal cells detected by the MFC method accounting for \< 0.1% of CD45-positive cells |
| Cmax | 28 days after CT1390B infusion | the peak of CARgene copy number in peripheral blood |
| Tmax | 28 days after CT1390B infusion | time to reach the peak of CARgene copy number in peripheral blood |
| AUC | 28 days after CT1390B infusion | area under curve of CARgene copy number in peripheral blood |
| Tlast | 28 days after CT1390B infusion | duration of existence of CARgene copy number in peripheral blood |
Countries
China
Contacts
CONTACTYing Wang, Dr
Outcome results
None listed