Clinical trial NCT06702098: Induced Pluripotent Stem Cells Derived Natural Killer Cells Therapy for Refractory and Relaps Acute Myelogenous Leukemia
Official title: Single-center and Single-arm Clinical Study of INK Cell Therapy for Relapsed and Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Keywords: iNK cells
R/R AML
iPSCs
Lead sponsor: Guangzhou Ruixin Biotechnological Co., LTD
Sponsor class: INDUSTRY
Collaborators: name: Fifth Affiliated Hospital of Guangzhou Medical University
First posted: 2024-11-22
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a clinical study on the use of iNK cells for the treatment of refractory relapsed acute myeloid leukemia.

Detailed description: Natural killer (NK) cells are lymphocytes of the innate immune system and could recognize and kill a wide range of cells in distress, particularly tumour cells and cells infected with viruses. Induced pluripotent setm cells(iPSCs) derived NK cells have better proliferative capacity and homogeneity than donor peripheral blood or umbilical cord blood derived NK cells. We conduct this clinical study to evaluate the efficacy and safety of INK cells in the treatment of acute myeloid leukemia and our purpose is to find new treatment option.

Eligibility criteria: Inclusion Criteria:

Patients must satisfy the following criteria to be enrolled in the study.

1. Patient is ≥ 18 and ≤ 80 years of age at the time of signing the Study informed consent form (ICF).
2. Patient understands and voluntarily signs the Study ICF prior to any study-related assessments/procedures are conducted.
3. Patient has eligible disease status:

   3.1 Primary or Secondary acute myeloid leukemia (AML) Patients in first of second Morphological Complete Remission (CR), Morphological Complete Remission with incomplete hematologic recovery (CRi), or Morphologic Leukemia-free State (MLFS) as defined by the European LeukemiaNet (ELN) recommendations for AML Response Criteria (Dohner, 2017).

   3.2 R/R diagnosis based on confirmed diagnosis with local pathology report following any reinduction/ salvage therapy ELN guidelines.

   3.2.1 Relapsed AML are defined as having relapsed after achieving ≥ 1 CR, including relapse after allogeneic stem cell transplantation (≥ 2 months after transplant).

   3.2.2 Refractory AML, defined as not achieving CR, CRi, or MLFS after 2 or more cycles of induction therapy (primary refractory) or not achieving CR after treatment for relapsed AML.

   3.2.3 Secondary AML (MDS transformation): Secondary AML patients are eligible to participate if they have received a minimum of one prior line of treatment for AML.

   3.2.4 Treatment-related AML: Treatment-related AML patients are eligible to participate if they have received a minimum of one prior line of treatment for AML.
4. No active infection.
5. No heart , liver and kidney functioninsufficiency.
6. No central nervous system leukemia.

Exclusion Criteria:

1. Subject meets one of the following criteria. 1.1History of CAR-T treatment with third degree CRS. 1.2 History of NK cell and CIK cell immunotherapy.
2. Serious cardiovascular and cerebrovascular diseases. 2.1 Severe heart rhythm or conduction abnormalities, corrected QT interval (QTc)≥480 ms.

   2.2 Complete left bundle branch block, second- or third-degree atrioventricular block; 2.3 Severe, uncontrolled cardiac arrhythmias requiring medication. 2.4 New York Heart Association (NYHA) class II or above congestive heart failure.

   2.5 Left ventricular ejection fraction (LVEF) \<50% in color Doppler echocardiography.

   2.6 History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, severe pericardial disease, ECG evidence of acute ischemic or active conduction system abnormalities within 6 months prior to recruitment.
3. Previous or present concomitant other malignancies (except for basal cell carcinoma of the skin, non-melanoma and non-melanoma, carcinoma in situ of the breast/cervix that have been effectively controlled, and other malignancies that have been effectively controlled without treatment in the past five years).
4. Uncontrollable systemic disease(e.g. uncontrolled hypertension, diabetes, etc).
5. Pregnant women, lactating females, patients who refuse to use effective contraception during the study.
6. history of severe neurological or psychiatric illness.
7. Positive for hepatitis B surface antigen.
8. Patients who are judged by the investigator to be unsuitable for participating in this study.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 12 months
measure: MRD negative rate
timeFrame: 12 months
measure: Progression-free Survival
timeFrame: 12 months
measure: Overall survival
timeFrame: 12 months
Secondary outcomes:
measure: Determination of chimerism of iNK cells in peripheral blood of subject.
timeFrame: 12 months
Other outcomes:
Locations:
city: Guangzhou city
country: China
facility: Guangzhou Ruixin Biotechnology Co., Ltd
state: Guangdong Province, China
Study officials:
affiliation: Fifth Affiliated Hospital of Guangzhou Medical University
name: Huo Tan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fifth Affiliated Hospital of Guangzhou Medical University
name: Runhui Zheng, MD
role: STUDY_DIRECTOR
References: