Safety and Preliminary Efficacy of JK500 Cell Injection in Relapsed/Refractory Pediatric Acute Myeloid Leukemia

Early Phase 1

Recruiting

• Conditions: Refractory Leukemia; Acute Myeloid Leukemia, Childhood; Relapsed Leukemia
• Interventions: Drug: JK500 cell injection，cyclophosphamide，Fludarabine

• Registration Number: NCT05519384
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Brief Summary

This study is a prospective, single-center, single-arm exploratory clinical study, aiming to complete the preliminary clinical observation of 12 children with relapsed/refractory acute myeloid leukemia treated with JK500 cell injection to evaluate the safety of clinical infusion and the initial efficacy of JK500 cell injection in the treatment of children with relapsed/refractory acute myeloid leukemia.

Detailed Description

The Main components of JK500 cell injection are regenerative natural killer (NK) cells derived from human embryonic stem cells and 0.9% sodium chloride solution.

Study Timeline

• Status Verified: 2022-08
• Study First Submitted: 2022-08-25
• Study First Submitted QC: 2022-08-25
• Study First Posted: 2022-08-29
• Study Start: 2022-09-14
• Last Update Submitted: 2022-11-23
• Last Update Posted: 2022-11-28
• Primary Completion: 2023-11
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Age ≤18, male or female;
2. Patients diagnosed as acute myeloid leukemia (AML) according to the revised World Health Organization (WHO) criteria in 2016;
3. Patients who failed to achieve CR after two standard-dose induction therapy or had recurrence within six months after CR;
4. The subject or the guardian of the subject must fully understand the purpose, nature, method and possible adverse reactions of the test, agree the subject as the subject, and sign the informed consent.

Exclusion Criteria

1. Acute promyelocytic leukemia, chronic myelocytic leukemia, acute mixed-cell leukemia or known central nervous system leukemia;

2. AML associated with congenital syndromes such as Down syndrome, Fanconi's anemia, Bloom's syndrome, Koch's syndrome, or congenital aplastic anemia;

3. The subjects have active virus infection, and during the screening period, the serum virology test is performed, and the human immunodeficiency virus (HIV) antibody is positive, hepatitis B surface antigen or E antigen is positive, hepatitis C antibody is positive, or treponema pallidum antibody is positive;

4. Presence of active systemic infection; Participated in a drug trial within the past 4 weeks;

5. Patients who suffered from a clinically significant disease within 28 days before receiving the study product or underwent a major surgical operation within 28 days before receiving the study product, or are expected to need major surgery during the trial;

6. children with liver and kidney dysfunction, including:

   1. Serum creatinine >2× upper limit of normal reference value;
   2. Serum total bilirubin > 2× upper limit of normal reference value;
   3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2× upper limit of normal reference values

7. Children who have used live attenuated vaccine 4 weeks before administration or plan to use live attenuated vaccine within 6 months after administration;

8. Have any other conditions that may cause the subject to be unable to complete the study or present a significant risk to the subject in the opinion of the Investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
JK500 cell injection	JK500 cell injection，cyclophosphamide，Fludarabine	They were divided into three dose groups: 10\^6, 5x10\^6 and 3x10\^7 JK500 cells injection /kg/ time, three times a week, a total of 6 times. According to the principle of dose escalation, 3 patients were assigned to each dose group. After completing the treatment of 3 patients in each dose group, the Safety Review Committee (SRC) discussed whether to enter the next dose group.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT)	28 days	DLT evaluation is defined as adverse events or laboratory abnormalities that occur within 4 weeks after investigational drug administration, are unrelated to external causes such as progressive disease, concomitant disease, and concomitant medications, including hematologic and non-hematologic adverse events (grade according to NCI CTCAE 5.0).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	24 months	ORR was defined as complete response (CR)+ incomplete bone marrow recovery (CRi) + partial response (PR). Treatment response will be assessed periodically until the end of treatment and up to 24 months after the first injection.
Minimal Residual Disease (MRD)	24 months	To observe the MRD status in bone marrow.

Trial Locations

Locations (1)

Department of Pediatrics, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Tianjin, Tianjin, China