Overview

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

Status:
Not yet recruiting
Trial end date:
2023-09-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Xinqiao Hospital of Chongqing
Collaborator:
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
Treatments:
Cyclophosphamide
Fludarabine
Criteria
Inclusion Criteria:

1. ECOG performance status score ≤ 2.

2. Life expectancy ≥ 12 weeks from the time of enrollment.

3. 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).

4. CD33 expression must be detected on greater than 50% of the malignant cells by
immunohistochemistry or greater than 80% by flow cytometry.

5. 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.

6. Without history of accepting anti-cancer therapy, including chemotherapy,
radiotherapy, immunotherapy (immune suppressive drugs or corticosteroid treatment)
within 4 weeks of screening.

7. Women of child-bearing age must have evidence of negative pregnancy test.

8. Subjects of reproductive potential must agree to use acceptable birth control methods
within 1 year after treatment, as described in protocol.

9. 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.

10. All participants must have the ability to understand and willingness to sign a written
informed consent.

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia (APL M3): t(15;17)(q22;q12); (promyelocytic
leukemia [PML]/retinoic acid receptor [RAR] alpha [a]) and variants excluded.

2. Active acute or chronic GVHD or requirement of immunosuppressant medications for GVHD
within 4 weeks of enrollment.

3. 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.

4. 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.

5. Sever illness or medical condition, which would not permit the patient to be managed
according to the protocol, including active uncontrolled infection.

6. Pregnant or lactating women.

7. 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.

8. 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.

9. Patients who suffer from allergies for any cytokines or antibodies.

10. Contraindications for fludarabine or cyclophosphamide treatment.

11. Receiving corticosteroids at >20 mg daily prednisone dose or equivalent.

12. Drug abuse and addiction.

13. History of mental disorders.

14. Other patients that researchers considered unsuitable for inclusion.