CD123-targeted CAR-NK cell therapy for certain types of leukemia

Clinical Study of Targeting CD123 Chimeric Antigen Receptor Natural Killer Cells (CAR-NK) in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm

This study is testing a new type of cell therapy for people with certain types of leukemia to see if it is safe and effective in treating their disease.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: CAR T, chemotherapy
• Locations: 1 site (Taiyuan, Shanxi)
• Trial ID: NCT06006403 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of CD123-targeted CAR-NK cell preparations in patients with relapsed or refractory acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). The study is structured in two parts: a dose exploration phase to determine the recommended dose and a dose expansion phase to further assess safety and efficacy. Patients are grouped based on their specific disease type, and the trial aims to gather pharmacokinetic data on the CAR-NK cell preparations used in treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with relapsed or refractory AML or BPDCN that express CD123.

Not a fit: Patients with CD123-negative tumors or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat forms of leukemia.

How similar studies have performed: Other studies utilizing CAR-NK cell therapies have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Gender is not limited, age 18-75 years old (including the threshold value);
2. The expression of CD123 in tumor cells was detected by flow cytometry.
3. Patients with relapsed/refractory AML or BPDCN diagnosed with CD123 positive: 1) AML: a. Recurrent: After complete response (CR), the recurrence of leukemia cells in peripheral blood or bone marrow original cells ≥5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or the occurrence of extramedullary leukemia cell infiltration; b. Refractory: refers to those who have failed to receive 2 courses of treatment with standard protocols; Patients recurrence within 12 months after CR with consolidation and intensive treatment; Recurrence after 12 months but failed to respond to conventional chemotherapy; 2 or more relapses; Extramedullary leukemia persists;

2\) BPDCN: has failed to receive guidelines-recommended salvage therapy or is unable to tolerate current therapy, and has persistent or recurrent disease in any of the peripheral blood, bone marrow, lymph nodes, spleen, skin lesions, or other site lesions.

4\. Expected survival time is more than 12 weeks;

5\. ECOG 0-2 points (Appendix 2);

6\. No serious mental disorders; The functions of important organs are basically normal:

1. Cardiac function: echocardiography indicated cardiac ejection fraction ≥50%, and no obvious abnormality was found in electrocardiogram;
2. Renal function: serum creatinine ≤2.0×ULN;
3. Liver function: ALT and AST ≤ 3.0×ULN;
4. Total bilirubin and alkaline phosphatase ≤ 2.0×ULN (Gilbert syndrome ≤ 3.0×ULN);
5. Blood oxygen saturation \> 92%.

   7\. The patient or his/her guardian agrees to participate in the clinical trial and signs the ICF, indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

Exclusion Criteria:

1. Prior to screening, the following anti-tumor therapies were received: chemotherapy, targeted therapy, or other investigational drug treatment within 14 days or at least 5 half-lives (whichever is shorter), except in cases where disease progression has been confirmed after treatment;
2. had a cerebrovascular accident or seizure within 6 months before signing the ICF;
3. There is an active or uncontrolled infection that requires systemic treatment within 1 week prior to screening;
4. suffering from any of the following heart diseases:

   1. New York Heart Association (NYHA) Stage III or IV congestive heart failure;
   2. Had myocardial infarction or coronary artery bypass grafting (CABG) within ≤6 months before enrollment;
   3. A history of clinically significant ventricular arrhythmia, or unexplained syncope (other than those caused by vasovagal or dehydration);
   4. History of severe non-ischemic cardiomyopathy;
5. combined with active hepatitis B;
6. Combined with active autoimmune diseases, long-term immunosuppressive therapy is required;
7. have other malignancies, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery;
8. Had received live attenuated vaccine within 4 weeks prior to screening;
9. Women who are pregnant or breastfeeding, and male or female subjects who plan to have a family within 1 year after receiving CAR T cell transfusion;
10. Circumstances deemed unsuitable for participation in the study by other researchers.

Where this trial is running

Taiyuan, Shanxi

• Shanxi Bethune Hospital — Taiyuan, Shanxi, China (Recruiting)

Study contacts

• Principal investigator: Jia Wei, M.D — Shanxi Bethune Hospital
• Study coordinator: Jia Wei, M.D

Conditions Acute Myeloid Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Relapse Leukemia; Refractory Leukemia