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

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.

Study Overview

• Status: Recruiting
• Conditions: Refractory Leukemia; Relapsed Leukemia; Acute Myeloid Leukemia, Childhood
• Intervention / Treatment: Drug: JK500 cell injection，cyclophosphamide，Fludarabine

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 Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Min Ruan, MD; Phone Number: +8613602177144; Email: ruanmin@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Department of Pediatrics, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences
      • Contact: Xiaofan Zhu, MD; Phone Number: 86-21-23909001; Email: xfzhu@ihcams.ac.cn
      • Sub-Investigator: Min Ruan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: JK500 cell injection; 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.

Drug: JK500 cell injection，cyclophosphamide，Fludarabine; After enrollment, patients received JK500 cell injection infusion after reinduction therapy. Pretreatment regimen before cell infusion: intravenous infusion of cyclophosphamide 60mg/kg day -7, intravenous infusion of fludarabine 25mg/㎡/day day -6 to -2 days. In order to activate and expand circulating NK cells, on the day of each infusion of JK500 cells, the patients were first subcutaneously injected with 100WU/ m2 of interleukin (IL)-2 0.5h-1h in advance, for a total of 6 doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	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).	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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.	24 months
Minimal Residual Disease (MRD)	To observe the MRD status in bone marrow.	24 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital
• Collaborators: Bejing Institute for Stem Cell and Regenerative Medicine; Institute for Stem cell and Regeneration, Chinese Academy of Sciences
• Investigators: Principal Investigator: Xiaofan Zhu, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2022
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 29, 2022

Study Record Updates

• Last Update Posted (Actual): November 28, 2022
• Last Update Submitted That Met QC Criteria: November 23, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: ISCRNK01001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No