To hear about similar clinical trials, please enter your email below
Trial Title:
Administration of Anti Tim-3/CD123 CAR-T Cell Therapy in Relapsed and Refractory Acute Myeloid Leukemia (rr/AML)
NCT ID:
NCT06125652
Condition:
Acute Myeloid Leukemia Refractory
Acute Myeloid Leukemia, in Relapse
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
anti Tim-3/CD123 CAR-T cell therapy
Description:
Enrolled patients will receive prespecified dose of autologous CAR-T cells.
Arm group label:
anti Tim-3/CD123 CAR-T cell therapy
Summary:
To evaluate the safety and efficacy of anti Tim3/CD123 CAR-T cells in the treatment of
relapsed and refractory acute myeloid leukemia.
Detailed description:
Cluster of Differentiation 123 (CD123) is usually overexpressed on leukemia stem cells
(LSCs) in acute myeloid leukemia (AML). However, CD123 has poor specificity and is also
expressed on normal hematopoietic stem cells (HSC), myeloid cells, and some
non-hematopoietic cells. This leads to widespread on-target off-tumor effect in the
clinical application of anti CD123 CAR-T cells, manifested as severe bone marrow
suppression, organ damage, and patients experiencing infections, bleeding, and organ
dysfunction. T cell immunoglobulin and mucin domain 3 (Tim-3) belongs to the Tim gene
family. 85% of LSCs highly express Tim-3, while normal hematopoietic stem/progenitor
cells (HSC/P), granulocytes, and macrophages do not express Tim-3. Compared with CD123,
seeing Tim-3 as a recognition tool for LSCs has higher specificity. In vivo and in vitro
studies have confirmed that anti Tim-3 CAR-T cells have significant anti LSCs effects,
while not affecting the ability of normal HSC/P to form colonies and differentiate
lineages. We believe that using both Tim-3 and CD123 as targets for CAR-T cells can
improve the specificity of recognizing LSCs, reduce the killing effect of CAR-T cells on
HSC/P expressing CD123, and thus reduce the on-target off-tumor effect.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. All subjects must sign and date the Informed Consent before initiating any study
specific procedures or activities;
2. At the age of 18-70 years old;
3. Diagnosed as relapse/refractory (r/r) de novo or secondary acute myeloid leukemia
(AML);
4. The patient has recovered from the toxicity of previous treatment;
5. ECOG score ≤ 2 and expected survival period is not less than 3 months;
6. Adequate organ function defined as:AST ≤3×ULN; ALT ≤3×ULN; Total bilirubin ≤1.5×ULN;
Serum creatinine ≤1.5×ULN, or CCR≥60 mL/min; Hemoglobin ≥60g/L ; Indoor oxygen
saturation ≥92%; LVEF≥45%;
7. Pregnancy testing: females of childbearing potential must have a negative serum or
urine pregnancy test;
8. From the use of study drug to 2 years after treatment, males and female of
childbearing potential must agree to use an effective method of contraception.
Exclusion Criteria:
1. Diagnosis of acute promyelocytic leukemia;
2. History or presence of a CNS disorder;
3. HBsAg is positive; HCV #HIV or Syphilis antibody are positive, CMV-DNA in peripheral
blood is more than≥500 copies /mL;
4. History of severe hypersensitivity reaction;
5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina,
New York Heart Association Class II or greater congestive heart failure, atrial
fibrillation, or other clinically significant cardiac disease within 12 months
before enrollment;
6. History of organ transplant surgery;
7. Required systemic application of immunosuppressive or other drugs;
8. Auto-SCT within the 3 months before enrollment;
9. Active autoimmune or inflammatory diseases of the nervous system (e.g.,
Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically
active cerebrovascular diseases (e.g., cerebral edema, posterior reversible
encephalopathy syndrome (PRES));
10. Requirement for urgent therapy due to ongoing or impending oncologic emergency (eg,
leukostasis or tumor lysis syndrome (TLS)) ;
11. Presence or suspicion of a fungal, bacterial, viral, or other infection that is
uncontrolled or requiring antimicrobials for management;
12. Live vaccine received within the ≤ 4 weeks before enrollment;
13. Persons with serious mental illness;
14. History of major surgical operations four weeks before enrollment;
15. History of alcoholism or substance abuse;
16. Was identified by the investigators as unsuitable to participate in the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Kailin Xu
Address:
City:
Xuzhou
Zip:
221000
Country:
China
Status:
Recruiting
Contact:
Last name:
Kailin Xu, M.D., Ph.D.
Phone:
15162166166
Email:
lihmd@163.com
Start date:
November 4, 2023
Completion date:
January 1, 2027
Lead sponsor:
Agency:
Xuzhou Medical University
Agency class:
Other
Source:
Xuzhou Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06125652
