Clinical Trial of CD123-targeted CAR-NK Therapy for Relapse/refractory AML or BPDCN

NCT06690827 | Recruiting Phase 1

• 1 other identifier: PBC065
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a clincal trial initiated by investigator to evaluate the safety and efficacy of anti-CD123 CAR-NK in the treatment of patients with relapsed/refractory acute myeloid leukemia or blastic plasma cell like dendritic cell tumors.

Conditions

AML (Acute Myeloid Leukemia); BPDCN (blastic Plasmacytoid Dendritic Cell Neoplasm)

Keywords

CD123; AML; Acute Myeloid Leukemia; blastic plasmacytoid dendritic cell neoplasm; acute leukemia; Malignant Hematoma; CAR-NK; CD123 CAR-NK; Chimeric antigen natural killer cells

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  The incidence of adverse events after CAR-NK cell infusion was assessed by CTCAE, version 5.0.

  28 dyas

• Objective response rate (ORR), including complete response (CR) and partial response (PR), after CAR-NK infusion

  1month, 2 months, 3 months

• overall survival (OS) after CAR-NK infusion

  2 years

• Duration of response (DOR) after CAR-NK infusion

  2 years

• recurrence free survival (RFS) after CAR-NK infusion

  2 years

• event free survival (EFS) after CAR-NK cells infusion

  2 years

Secondary Outcomes (9)

• Dose limited toxicity (DLT) rate after CAR-NK infusion

  1 month

• Cmax of anti-CD123 CAR-NK cells in humans

  1 month

• Overall response rate (ORR) after anti-CD123 CAR-NK therapy in relapsed/refractory AML and BPDCN patients

  1 year

• Tmax of anti-CD123 CAR-NK cells [Cell dynamics]

  1 month

• AUCs of anti-CD123 CAR-NK cells [Cell dynamics]

  1 month

Study Arms (1)

CD123 CAR-NK cells

EXPERIMENTAL

Drug: Anti-CD123 CAR NK cells

Interventions

Anti-CD123 CAR NK cells DRUG

Each patient will receive two CAR-NK cell infusions at D0 and D7, and CAR-NK cells need to be controlled within 70 minutes from thawing to infusion completion.

CD123 CAR-NK cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of any gender, aged between 18 and 75 years (inclusive);
• Positive expression of CD123 on tumor cells detected by flow cytometry;
• Patients with a confirmed diagnosis of CD123-positive relapsed/refractory AML or BPDCN:
• (1) For AML patients：
• Relapsed refers to the reappearance of leukemic cells in peripheral blood after complete remission (CR), or ≥5% blasts in bone marrow (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy), or the presence of leukemic cell infiltration outside the marrow;
• Refractory refers to patients who have not responded to two courses of standard treatment; patients who have relapsed within 12 months after CR and consolidation/intensification therapy; patients who have relapsed after 12 months but have not responded to conventional chemotherapy; patients with two or more relapses; patients with persistent extramedullary leukemia;
• (2) For BPDCN patients: Patients who have not responded to or cannot tolerate the recommended salvage treatment according to guidelines, and have persistent or recurrent disease in any of the following: peripheral blood, bone marrow, lymph nodes, spleen, skin lesions, or other sites.
• \. Expected survival time of more than 12 weeks;
• \. ECOG score of 0-2 (Appendix 2);
• \. No severe mental disorders;
• \. Basic normal function of important organs:
• Blood routine: white blood cells \>1.0×109/L, neutrophils \>0.5×109/L, lymphocytes \>0.5×109/L, platelets \>50×109/L;
• Cardiac function: echocardiography indicates a left ventricular ejection fraction ≥50%, and no significant abnormalities on electrocardiogram;
• Renal function: serum creatinine ≤2.0×ULN;
• Liver function: ALT and AST ≤3.0×ULN (for patients with liver invasion

You may not qualify if:

• Presence of active central nervous system invasion during screening;
• Receipt of anti-tumor therapies prior to screening, including chemotherapy, targeted therapy, or other experimental drug treatments within 14 days or at least 5 half-lives (whichever is shorter), except for those who have confirmed disease progression after treatment;
• Occurrence of cerebrovascular accident or epileptic seizure within 6 months prior to screening;
• Presence of active or uncontrolled infection requiring systemic treatment within 1 week prior to screening;
• Presence of any of the following cardiac diseases:
• Congestive heart failure at New York Heart Association (NYHA) class III or IV;
• Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months prior to enrollment;
• Clinically significant ventricular arrhythmia, or history of unexplained syncope (excluding cases caused by vasovagal or dehydration);
• History of severe non-ischemic cardiomyopathy;
• Combination with active autoimmune diseases requiring long-term immunosuppressive therapy;
• Presence of other malignancies, except for adequately treated carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin, localized prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery.
• Receipt of live attenuated vaccines within 4 weeks prior to screening;
• Pregnant or breastfeeding women, as well as male or female subjects who plan to have children within 1 year after receiving CAR-NK cell infusion;
• Other conditions that the investigator deems unsuitable for participation in the study.

Sponsors & Collaborators

• Chongqing Precision Biotech Co., Ltd: lead

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology.

Wuhan, Hubei, 430030, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Blastic Plasmacytoid Dendritic Cell Neoplasm

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Wei Jia, Professor

CONTACT

+86 13986102084; jiawei@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2024
• First Posted: November 15, 2024
• Study Start: November 13, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2028
• Last Updated: November 15, 2024

Record last verified: 2024-11

Locations

CN (1)