Anti-CD33 CAR NK Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

NCT05008575 | Unknown Phase 1

• 1 other identifier: CD33 CAR NK-AML
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

CAR technology has been used in T cell therapy and gets great success in treating hematological diseases. Following models of CAR T cells, CAR NK cell therapy has been one hot point. For myeloid malignancies, CD33 is widely expressed. Targeting CD33 surface antigens by CAR NK cells provides an off-the-shelf immune cell therapy.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (2)

• Overall Remission Rate (ORR)

  Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CRi), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies

  4 weeks after infusion

• incidence of participants with dose limiting toxicity (DLT)

  To characterize the safety, tolerability of Anti-CD33 CAR NK cells

  within 4 weeks after infusion

Secondary Outcomes (3)

• Progression-free survival (PFS)

  up to 2 years after infusion

• Overall Response Rate (ORR)

  up to 2 years after infusion

• Overall survival(OS)

  up to 2 years after infusion

Study Arms (1)

antiCD33 CAR NK cells

EXPERIMENTAL

After preconditioning with chemotherapy, the antiCD33 CAR NK cells will be evaluated

Biological: anti-CD33 CAR NK cells; Drug: Fludarabine; Drug: Cytoxan

Interventions

anti-CD33 CAR NK cells BIOLOGICAL

6×10\^8, 12×10\^8, 18×10\^8/KG Treatment follows a lymphodepletion

antiCD33 CAR NK cells

Fludarabine DRUG

recommendation: 30mg/m2 (D-5\~D-3),determined by tumor burden at baseline.

antiCD33 CAR NK cells

Cytoxan DRUG

recommendation: 300-500mg/m2 (D-5\~D-3),determined by tumor burden at baseline.

antiCD33 CAR NK cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG performance status score ≤ 2.
• Life expectancy ≥ 12 weeks from the time of enrollment.
• Disease status at the time of enrollment: -Patients with AML (except M3) who have not achieved complete remission after standard chemotherapy regimens; -Not suitable or unconditional for allogeneic hematopoietic stem cell transplantation; -Patients with recurrent acute myeloid leukemia after autologous hematopoietic stem cell transplantation without active graft-versus-host disease (GVHD).
• CD33 expression must be detected on greater than 50% of the malignant cells by immunohistochemistry or greater than 80% by flow cytometry.
• Adequate main organ function as assessed by the following laboratory requirements: creatinine ≤ 2.5 × upper limit of normal, cardiac ejection fraction ≥ 40%, oxygen saturation ≥ 90%, total bilirubin ≤ 3 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, Hgb≥80g/L.
• Without history of accepting anti-cancer therapy, including chemotherapy, radiotherapy, immunotherapy (immune suppressive drugs or corticosteroid treatment) within 4 weeks of screening.
• Women of child-bearing age must have evidence of negative pregnancy test.
• Subjects of reproductive potential must agree to use acceptable birth control methods within 1 year after treatment, as described in protocol.
• After discussion by the expert group, the patient's condition was analyzed and combined with the general physical condition of the patient, the benefit of participating in the clinical trial was greater than the risk.
• All participants must have the ability to understand and willingness to sign a written informed consent.

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia (APL M3): t(15;17)(q22;q12); (promyelocytic leukemia \[PML\]/retinoic acid receptor \[RAR\] alpha \[a\]) and variants excluded.
• Active acute or chronic GVHD or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
• Have been diagnosed with or treated other malignant tumors other than AML within 5 years before screening, except for the following conditions: participants with adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer; or received radical treatment Local prostate cancer, ductal carcinoma in situ.
• There are serious systemic diseases: New York Heart Association (NYHA) stage III or IV congestive heart failure; cerebrovascular accident or myocardial infarction or hemodynamic instability caused by arrhythmia within 6 months before signing the informed consent; impaired cardiac function (LVEF\<50%) assessed by echocardiographic scan.
• Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
• Pregnant or lactating women.
• Subjects with radiologically-detected CNS chloromas or CNS 3 disease (presence of ≥ 5/μL white blood cells (WBCs) in cerebral spinal fluid (CSF) and cytospin positive for blasts \[in the absence of a traumatic lumbar puncture\] and/or clinical signs of CNS leukemia such as a cranial nerve palsy from active disease). Subjects with adequately treated CNS leukemia are eligible.
• Human immunodeficiency virus (HIV) seropositivity; hepatitis B surface antigen is positive or HBV DNA is higher than the detection limit of the analysis method; hepatitis C antibody is positive or HCV RNA is higher than the detection limit of the analysis method; syphilis antibody and syphilis rapid plasma reagin are positive; CMV DNA is positive.
• Patients who suffer from allergies for any cytokines or antibodies.
• Contraindications for fludarabine or cyclophosphamide treatment.
• Receiving corticosteroids at \>20 mg daily prednisone dose or equivalent.
• Drug abuse and addiction.
• History of mental disorders.

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead
• Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Department of Hematology, Xinqiao Hospital

Chongqing, Chongqing Municipality, 400037, China

RECRUITING

Related Publications (1)

• Huang R, Wang X, Yan H, Tan X, Ma Y, Wang M, Han X, Liu J, Gao L, Gao L, Jing G, Zhang C, Wen Q, Zhang X. Safety and efficacy of CD33-targeted CAR-NK cell therapy for relapsed/refractory AML: preclinical evaluation and phase I trial. Exp Hematol Oncol. 2025 Jan 2;14(1):1. doi: 10.1186/s40164-024-00592-6.

  PMID: 39748428 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• xi zhang, MD/PhD

  Department of Hematology, Xinqiao Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xi zhang, MD/PhD

CONTACT

13808310064; zhangxxi@sina.com

ruihao huang, MD

CONTACT

18984398751; 1169731117@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chef of hemotology department

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: August 14, 2021
• First Posted: August 17, 2021
• Study Start: December 23, 2021
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: January 12, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)