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

NCT ID: NCT05563545

Last Updated: 2022-11-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-21
• Study Completion Date: 2022-11-25

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.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAR-NK-CD19 Cells

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

Group Type: EXPERIMENTAL

CAR-NK-CD19 Cells

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hebei Yanda Ludaopei Hospital

OTHER

Sponsor Role: collaborator

Shanghai Simnova Biotechnology Co.,Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hebei Yanda Ludaopei Hospital

Sanhe, Hebei, China

Countries

China

Other Identifiers

XB-NK-1003

Identifier Type: -

Identifier Source: org_study_id