Clinical trial NCT05563545: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
Keywords: NK
CD19 positive
Acute B lymphoblastic leukemia
Lead sponsor: Shanghai Simnova Biotechnology Co.,Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Hebei Yanda Ludaopei Hospital
First posted: 2022-10-03
Enrollment: 2
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety of CAR NK-CD19 Cell
timeFrame: Up to 3 months after cell infusion
measure: Cell count of CAR NK-CD19
timeFrame: From 1 to 720 days after infusion
measure: Cmax of CAR NK-CD19
timeFrame: From 1 to 720 days after infusion
measure: Tmax of CAR NK-CD19
timeFrame: From 1 to 720 days after infusion
measure: AUC of CAR NK-CD19
timeFrame: From 1 to 720 days after infusion
measure: Other pharmacokinetic of CAR NK-CD19 Cell
timeFrame: From 1 to 720 days after infusion
Secondary outcomes:
measure: The overall response rate (ORR)
timeFrame: Up to 3 months after cell infusion
measure: Concentration of anti-drug antibody (ADA)
timeFrame: From 14 to 720 days after infusion
measure: The changes of cytokines
timeFrame: Up to 3 months after cell infusion
Other outcomes:
Locations:
city: Sanhe
country: China
facility: Hebei Yanda Ludaopei Hospital
state: Hebei
Study officials:
References: