Anti-CD19 CAR-Engineered NK Cells in the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia

Phase 1

Completed

• Conditions: Acute Lymphoblastic Leukemia
• Interventions: Biological: CAR-NK-CD19 Cells

• Registration Number: NCT05563545
• Lead Sponsor: Shanghai Simnova Biotechnology Co.,Ltd.

Brief Summary

This study is a single arm clinical study to observe the safety ，dose tolerance and pharmacokinetic characteristics of CAR NK-CD19 in patients with recurrent or refractory CD19 positive acute lymphoblastic leukemia, and preliminarily evaluate the effectiveness, the immunogenicity of the product and the correlation between the changes of cytokines after infusion and CRS , ICANS.

Detailed Description

It is planned to select 9-21 patients with recurrent or refractory CD19 positive acute lymphoblastic leukemia （ALL）, from the lowest dose group. It is expected that 3-6 cases will be enrolled in each dose group. The protocol will be performed into screening period (-30\~-10 days), prophase of lymophodepletion (-10\~-5 days), Lymophodepletion (-5\~-3 days), pre-infusion evaluation (-2\~-1 days), infusion (day 0), and follow-up period (1-720 days). The incidence of DLT is observed after infusion. There are three preset dose groups in this clinical trial. The initial dose is 1.0 × 107 CAR positive NK cells/kg (body weight). Subsequent dose groups included 2.0 × 107 and 3.0 × 107 CAR positive NK cells/kg (body weight). The specific dose is determined by SRC based on the patient safety data and PK data. The maximum sample size of this study is tentatively 21 cases.

Study Timeline

• Study Start: 2022-07-21
• Status Verified: 2022-09
• Study First Submitted: 2022-09-26
• Study First Submitted QC: 2022-09-29
• Study First Posted: 2022-10-03
• Last Update Submitted: 2022-11-24
• Primary Completion: 2022-11-25
• Study Completion: 2022-11-25
• Last Update Posted: 2022-11-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Age ≥12 years in the single-dose exploration phase, age ≥3 years in the dose exploration phase, both sexes;
• Meet the diagnostic criteria for recurrent or refractory CD19 positive acute lymphoblastic leukemia.
• The main organs have good organ function.
• The estimated survival time is ≥12 weeks.
• Blood pregnancy tests for women of childbearing age are negative.
• The patient himself/herself , and/or his/her legal guardian, agree to participate in the trial and sign the informed consent form.

Exclusion Criteria

• Central nervous system involvement；
• Simple extramedullary leukemia or simple extramedullary recurrence；
• Received hematopoietic stem cell transplantation within the last 3 months and had graft-versus-host disease (GVHD) in the last 2 weeks, requiring immunosuppressive agents；
• Treated with high-dose corticosteroids in the last 1 week；
• Allogeneic cell therapy, major surgery, and live or attenuated vaccine had been received within 4 weeks prior to CAR NK-CD19 infusion；
• Had received other antitumor therapy or had an uncontrolled infection within 2 weeks prior to CAR NK-CD19 infusion；
• Systemic steroids were used within 3 days before CAR NK-CD19 infusion；
• Toxicity caused by previous treatment do not fully recover or do not stabilize to grade 1；
• Concomitant autoimmune diseases, central nervous system diseases, other active malignancies, infectious diseases, severe cardiovascular diseases, etc；
• Known allergies to study drugs or drugs that may be used in the study；
• Other conditions determined by Investigator which are not suitable for participation in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-NK-CD19 Cells	CAR-NK-CD19 Cells	After preconditioning with chemotherapy, CAR-NK-CD19 Cells will be evaluated.

Primary Outcome Measures

Name	Time	Method
Safety of CAR NK-CD19 Cell	Up to 3 months after cell infusion	Incidence of adverse events associated with CAR NK-CD19 treatment, abnormal clinically significant laboratory findings, including dose-limiting toxicity (DLT) and maximum-tolerated Dose (MTD).
Cell count of CAR NK-CD19	From 1 to 720 days after infusion	CAR NK-CD19 cell count
Cmax of CAR NK-CD19	From 1 to 720 days after infusion	CAR gene copy number maximum (Cmax)
Tmax of CAR NK-CD19	From 1 to 720 days after infusion	Time to maximum (Tmax)
AUC of CAR NK-CD19	From 1 to 720 days after infusion	Area under curve (AUC)
Other pharmacokinetic of CAR NK-CD19 Cell	From 1 to 720 days after infusion	Other related pharmacokinetic parameters in peripheral blood and bone marrow

Secondary Outcome Measures

Name	Time	Method
The overall response rate (ORR)	Up to 3 months after cell infusion	Total response rate (ORR) in 12 weeks (inclusive) after infusion of CAR NK-CD19 cells. CR/CRi ratio at 4 and 12 weeks; Duration of response (DOR); Progression free survival (PFS); Minimal residual disease (MRD) negative rate and duration at 4 and 12 weeks; Overall survival (OS)
Concentration of anti-drug antibody (ADA)	From 14 to 720 days after infusion	Detection of anti-drug antibody (ADA) in CAR NK-CD19 cells
The changes of cytokines	Up to 3 months after cell infusion	Detect the changes of cytokines in peripheral blood before and after CAR NK-CD19 cell infusion and the recovery time

Trial Locations

Locations (1)

Hebei Yanda Ludaopei Hospital; 🇨🇳 Sanhe, Hebei, China