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

Primary Purpose

Acute Lymphoblastic Leukemia

Status

Completed

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

CAR-NK-CD19 Cells

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring NK, CD19 positive, Acute B lymphoblastic leukemia

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hebei Yanda Ludaopei Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-NK-CD19 Cells

Arm Description

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

Outcomes

Primary Outcome Measures

Safety of CAR NK-CD19 Cell

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

CAR NK-CD19 cell count

Cmax of CAR NK-CD19

CAR gene copy number maximum (Cmax)

Tmax of CAR NK-CD19

Time to maximum (Tmax)

AUC of CAR NK-CD19

Area under curve (AUC)

Other pharmacokinetic of CAR NK-CD19 Cell

Other related pharmacokinetic parameters in peripheral blood and bone marrow

Secondary Outcome Measures

The overall response rate (ORR)

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)

Detection of anti-drug antibody (ADA) in CAR NK-CD19 cells

The changes of cytokines

Detect the changes of cytokines in peripheral blood before and after CAR NK-CD19 cell infusion and the recovery time

Full Information

NCT ID

NCT05563545

First Posted

September 26, 2022

Last Updated

November 24, 2022

Sponsor

Shanghai Simnova Biotechnology Co.,Ltd.

Collaborators

Hebei Yanda Ludaopei Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05563545

Brief Title

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

Official Title

A Phase Ⅰ Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor Gene Modified NK Cells Targeting CD19 in Patients With Recurrent or Refractory CD19 Positive Acute Lymphoblastic Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Completed

Study Start Date

July 21, 2022 (Actual)

Primary Completion Date

November 25, 2022 (Actual)

Study Completion Date

November 25, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Simnova Biotechnology Co.,Ltd.

Collaborators

Hebei Yanda Ludaopei Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphoblastic Leukemia

Keywords

NK, CD19 positive, Acute B lymphoblastic leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CAR-NK-CD19 Cells

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

CAR-NK-CD19 Cells

Intervention Description

CAR-NK-CD19 Cells, 1-3×10^7 /KG, treatment follows a lymphodepletion. Drug: Fludarabine Recommendation: 25-30 mg/m2 (D-5~D-3), determined by tumor burden at baseline. Drug: Cyclophosphamide Recommendation: 250-300 mg/m2 (D-5~D-3), determined by tumor burden at baseline.

Primary Outcome Measure Information:

Title

Safety of CAR NK-CD19 Cell

Description

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).

Time Frame

Up to 3 months after cell infusion

Title

Cell count of CAR NK-CD19

Description

CAR NK-CD19 cell count

Time Frame