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

Acute Lymphoblastic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05563545
• Other study ID #: XB-NK-1003
• Status: Completed
• Phase: Phase 1
• Start date: July 21, 2022
• Est. completion date: November 25, 2022

Study information

• Verified date: September 2022
• Source: Shanghai Simnova Biotechnology Co.,Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: November 25, 2022
• Est. primary completion date: November 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• CAR-NK-CD19 Cells
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.

Locations

Country	Name	City	State
China	Hebei Yanda Ludaopei Hospital	Sanhe	Hebei

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Simnova Biotechnology Co.,Ltd.	Hebei Yanda Ludaopei Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Up to 3 months after cell infusion
Primary	Cell count of CAR NK-CD19	CAR NK-CD19 cell count	From 1 to 720 days after infusion
Primary	Cmax of CAR NK-CD19	CAR gene copy number maximum (Cmax)	From 1 to 720 days after infusion
Primary	Tmax of CAR NK-CD19	Time to maximum (Tmax)	From 1 to 720 days after infusion
Primary	AUC of CAR NK-CD19	Area under curve (AUC)	From 1 to 720 days after infusion
Primary	Other pharmacokinetic of CAR NK-CD19 Cell	Other related pharmacokinetic parameters in peripheral blood and bone marrow	From 1 to 720 days after infusion
Secondary	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)	Up to 3 months after cell infusion
Secondary	Concentration of anti-drug antibody (ADA)	Detection of anti-drug antibody (ADA) in CAR NK-CD19 cells	From 14 to 720 days after infusion
Secondary	The changes of cytokines	Detect the changes of cytokines in peripheral blood before and after CAR NK-CD19 cell infusion and the recovery time	Up to 3 months after cell infusion