Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06027853
Other study ID # QH-CLL1-01
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date September 10, 2023
Est. completion date August 31, 2026

Study information

Verified date August 2023
Source Zhejiang University
Contact He Huang, MD
Phone +8613605714822
Email hehuangyu@126.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the safety, tolerability and preliminary efficacy of CLL1 target CAR iPSC NK cells in patients with relapsed/refractory AML


Description:

Acute myelogenous leukemia (AML) is a potentially cur-able disease; 70% of newly diagnosed patients achievecomplete remission with first-line therapy, but prognosisworsens for relapsed disease in both pediatric and adultpatients. CLL-1 has attracted the researchers' attention due to its high expression in AML while being absent in normal hematopoietic stem cell. Accumulating evidence have demonstrated CLL-1 is an ideal target for AML.


Recruitment information / eligibility

Status Recruiting
Enrollment 24
Est. completion date August 31, 2026
Est. primary completion date August 31, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. =18 years old. 2. Confirmed diagnosis of r/r AML 3. CLL1 expression is positive in AML blasts. 4. Eastern Cooperative Oncology Group (ECOG) performance status =1 and life expectancy greater than 12 weeks. 5. Adequate organ and marrow function, as defined below: 1. Blood creatinine (Cr) = 2 x ULN or calculated creatinine clearance (Cockcroft- Gault formula) = 50 mL/min; 2. Total bilirubin (TBIL) = 2 x the ULN; 3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x ULN; 4. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) = 1.5 x ULN 6. Females of childbearing potential must have a negative serum pregnancy test. 7. Donor specific antibody (DSA) is negative: MFI <= 2000. 8. Provision of signed and dated informed consent form (ICF). Exclusion Criteria: 1. Allergic to drug used in this study. 2. Subjects received any antitumor therapy as follows, prior to first NK infusion: 1. Systemic steroid therapy within 3 days (except physiological replacement therapy); 2. Systemic antitumor therapy within 2 weeks or at least 5 half-lives, whichever is less; 3. Radiotherapy within 4 weeks; 4. Donor lymphocyte infusion within 6 weeks; 5. Intrathecal treatment within 1 week; 6. CAR-T therapy, CAR-NK therapy, or any other genetically modified cell therapy product within 6 months; 3. History of allogeneic stem cell transplantation. 4. Received the vaccine within 4 weeks prior to the first infusion and/or expected to require vaccination from the study period to 12 weeks after the last infusion. 5. Active central nervous system Leukemia. 6. Acute Promyelocytic Leukemia (APL). 7. History of other malignant tumors, except for those who have achieved complete remission more than 5 years after radical treatment without any signs of recurrence. 8. Active autoimmune diseases. 9. History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc. 10. Serious cardiovascular and cerebrovascular diseases: 1. Severe heart rhythm or conduction abnormalities, corrected QT interval (QTc)=480 ms; 2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to first infusion; 3. New York Heart Association (NYHA) class II or above congestive heart failure or left ventricular ejection fraction (LVEF) <50% in color Doppler echocardiography; 4. Hypertension that cannot be controlled by drug. 11. Active pulmonary infection; SpO2 =90%; Pulmonary embolism, chronic obstructive pulmonary disease, or interstitial lung disease. 12. Uncontrolled bacterial, fungal, or viral infection. Known HIV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection. 13. History of substance abuse. 14. Toxicity induced by previous therapy not recovered to = grade 2(NCI-CTCAE v5.0). 15. Large surgical treatment within 4 weeks prior to first infusion, not including diagnostic biopsy. 16. Pregnant/breastfeeding women. 17. Investigator-assessed presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
CLL1 CAR-NK cell injection
Drug: CLL1 NK cell therapy Drug: Cyclophosphamid Lympho-conditioning Agent Drug: Fludarabine Lympho-conditioning Agent Drug: VP-16 Lympho-conditioning Agent

Locations

Country Name City State
China Clinical research ethics committee of the first affiliated hospital, college of medicine, zhejiang University Hangzhou Zhejiang

Sponsors (2)

Lead Sponsor Collaborator
Zhejiang University Hangzhou Qihangene Biotech Co.,Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of Treatment-Emergent Adverse Events Safety and Tolerability 28 Days from first dose of iPSC NK cell infusion
Primary Incidence of subjects with Dose Limiting Toxicities within each dose level cohort Tolerability 28 Days from first dose of iPSC NK cell infusion
Secondary Determination of the pharmacokinetics (PK) of iPSC NK cells in peripheral blood The PK of iPSC NK in peripheral blood will be reported as the relative percentage of product DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points Up to approximately 2 years after last dose of iPSC NK cell infusion
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04623944 - NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS Phase 1
Not yet recruiting NCT06313437 - Revumenib in Combination With 7+3 + Midostaurin in AML Phase 1
Terminated NCT04079738 - Study Augmenting TAK-659 Action in Relapsed/Refractory AML by Addition Ofthe Proteasome Inhibitor Ixazomib Phase 1/Phase 2
Recruiting NCT06052813 - A Study of BN104 in the Treatment of Acute Leukemia Phase 1/Phase 2
Completed NCT02986620 - Italian Registry on the Prevalence of IDH1/IDH2 Mutations in Patients With Acute Myeloid Leukemia
Recruiting NCT05601466 - Natural Killer(NK) Cell Therapy for Acute Myeloid Leukemia Phase 1
Recruiting NCT06066905 - A Study of Chidamide With AZA in MRD Positive AML After Transplant N/A
Recruiting NCT05909501 - Assessment of Geriatric Evaluations Impact on New AML Guidance
Terminated NCT04614636 - FT538 in Subjects With Advanced Hematologic Malignancies Phase 1
Not yet recruiting NCT06420063 - Sequential CAR-T Cells Targeting CD33/CD123 in Patients With Acute Myelocytic Leukemia AML Phase 1/Phase 2
Withdrawn NCT04128020 - Azacitidine Plus Nivolumab Following Reduced-intensity Allogeneic PBSC Transplantation for Patients With AML and High-risk Myelodysplasia Phase 1
Active, not recruiting NCT04749355 - Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS Phase 2
Active, not recruiting NCT04755244 - A Study of Evorpacept (ALX148) With Venetoclax and Azacitidine for Acute Myeloid Leukemia (ASPEN-05) Phase 1/Phase 2
Completed NCT03194685 - Study of FF-10101-01 in Patients With Relapsed or Refractory Acute Myeloid Leukemia Phase 1/Phase 2
Recruiting NCT03884829 - A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS Phase 1
Active, not recruiting NCT05177731 - Venetoclax + Decitabine vs. "7+3" Induction Chemotherapy in Young AML Phase 3
Not yet recruiting NCT06377579 - OBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia
Recruiting NCT05025098 - Precision Therapy Versus Standard Therapy in AML and MDS in Elderly Phase 2
Not yet recruiting NCT06263387 - Results From a French Temporary Utilization Authorization of First-line Acute Myeloid Leukemia (AML) Patients Ineligible for Intensive Chemotherapy (IC), Treated With Venetoclax Azacitidine
Not yet recruiting NCT06297772 - Compare the Efficacy and Safety of Dec-FB4 and FB4 as Conditioning Regimen for AML-MR Phase 3