Acute Lymphoblastic LeukemiaPhase 1NCT05563545
Anti-CD19 CAR-Engineered NK Cells in the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia
A Phase 1 study testing CAR-NK-CD19 Cells in people with Acute Lymphoblastic Leukemia, run by Shanghai Simnova Biotechnology Co.,Ltd. at 1 site in China.
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… Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- CAR-NK-CD19 Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteChina
- Study dates
- 21 Jul 2022to 25 Nov 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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；
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- CAR-NK-CD19 Cells
- Keywords
- NK, CD19 positive, Acute B lymphoblastic leukemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-NK-CD19 CellsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| CAR-NK-CD19 Cells | Experimental | After preconditioning with chemotherapy, CAR-NK-CD19 Cells will be evaluated. Receives: Biological: CAR-NK-CD19 Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 3 months after cell infusion
Cell count of CAR NK-CD19
CAR NK-CD19 cell count
Measured: From 1 to 720 days after infusion
Cmax of CAR NK-CD19
CAR gene copy number maximum (Cmax)
Measured: From 1 to 720 days after infusion
Tmax of CAR NK-CD19
Time to maximum (Tmax)
Measured: From 1 to 720 days after infusion
AUC of CAR NK-CD19
Area under curve (AUC)
Measured: From 1 to 720 days after infusion
Other pharmacokinetic of CAR NK-CD19 Cell
Other related pharmacokinetic parameters in peripheral blood and bone marrow
Measured: From 1 to 720 days after infusion
Secondary outcomes (3)
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)
Measured: Up to 3 months after cell infusion
Concentration of anti-drug antibody (ADA)
Detection of anti-drug antibody (ADA) in CAR NK-CD19 cells
Measured: From 14 to 720 days after infusion
The changes of cytokines
Detect the changes of cytokines in peripheral blood before and after CAR NK-CD19 cell infusion and the recovery time
Measured: Up to 3 months after cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2022
- Study start21 Jul 2022
- Primary completion25 Nov 2022
- Study completion25 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Simnova Biotechnology Co.,Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hebei Yanda Ludaopei Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05563545
- Sponsor's protocol ID
- XB-NK-1003
- Status last verified
- Sep 2022
- First submitted
- 26 Sep 2022
- Last updated
- 28 Nov 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05563545
- Acronym / sponsor ID
- XB-NK-1003
- Conditions
- Acute Lymphoblastic Leukemia
- Keywords
- NK, CD19 positive, Acute B lymphoblastic leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Shanghai Simnova Biotechnology Co.,Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Hebei Yanda Ludaopei Hospital
- Study start
- 21 Jul 2022 (actual)
- Primary completion
- 25 Nov 2022 (actual)
- Study completion
- 25 Nov 2022 (actual)
- First posted
- 3 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-NK-CD19 Cells | Experimental | Biological: CAR-NK-CD19 CellsAfter preconditioning with chemotherapy, CAR-NK-CD19 Cells will be evaluated. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (11 listed)
- 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；
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAR-NK-CD19 CellsCAR-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. | Biological | CAR-NK-CD19 Cells |
Primary outcome
Safety of CAR NK-CD19 Cell
Time frame: 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
Time frame: From 1 to 720 days after infusion
CAR NK-CD19 cell count
Cmax of CAR NK-CD19
Time frame: From 1 to 720 days after infusion
CAR gene copy number maximum (Cmax)
Tmax of CAR NK-CD19
Time frame: From 1 to 720 days after infusion
Time to maximum (Tmax)
AUC of CAR NK-CD19
Time frame: From 1 to 720 days after infusion
Area under curve (AUC)
Other pharmacokinetic of CAR NK-CD19 Cell
Time frame: From 1 to 720 days after infusion
Other related pharmacokinetic parameters in peripheral blood and bone marrow
3 secondary outcomes
The overall response rate (ORR)
Time frame: Up to 3 months after cell infusion
Concentration of anti-drug antibody (ADA)
Time frame: From 14 to 720 days after infusion
The changes of cytokines
Time frame: Up to 3 months after cell infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAR-NK-CD19 Cells in people with Acute Lymphoblastic Leukemia, run by Shanghai Simnova Biotechnology Co.,Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of CAR NK-CD19 Cell (time frame: Up to 3 months after cell infusion). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2022.