Acute Lymphoblastic Leukemia
Conditions
Keywords
NK, CD19 positive, Acute B lymphoblastic leukemia
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.
Interventions
BIOLOGICALCAR-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.
Sponsors
Hebei Yanda Ludaopei Hospital
Shanghai Simnova Biotechnology Co.,Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Other pharmacokinetic of CAR NK-CD19 Cell | From 1 to 720 days after infusion | Other related pharmacokinetic parameters in peripheral blood and bone marrow |
| 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) |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
Countries
China
Outcome results
None listed