Acute Myeloid LeukemiaEarly Phase 1NCT05215015
Study of Anti-CD33/CLL1 CAR-NK in Acute Myeloid Leukemia
A Early Phase 1 study testing Anti-CD33/CLL1 CAR-NK Cells in people with Acute Myeloid Leukemia, run by Wuxi People's Hospital at 1 site in China.
Trial summary
This is an open-label, nonrandomized, investigator-initiated clinical trial to evaluate the safety, tolerability, pharmacokinetics, and efficacy of anti-CD33/CLL1 CAR-NK cell injection in patients with acute myeloid leukemia (AML), and to determine PK parameters, maximum tolerated dose (MTD), and phase II recommended… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Anti-CD33/CLL1 CAR-NK Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 30 Nov 2020to 30 Nov 2022
- Phase
- Early 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects should voluntarily participate in this clinical study, are fully aware of the study, have signed the Informed Consent Forms, and are willing to follow and able to complete all trial procedures.
- Subjects who are more than 18 years old (including 18 years old), and less than 75 years old (including 75 years old);
- Subjects who are diagnosed as AML according to the World Health Organization (WHO) 2016 diagnosis criteria, and meet any of the following:
- Relapsed acute myeloid leukemia: after complete response (CR), there are leukemia cells in peripheral blood or blast cells in bone marrow >5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration.
- Refractory acute myeloid leukemia: treatment-naive subjects who have no response to the standard of care for 2 courses of treatment; subjects who are relapsed within 12 months with consolidated intensive treatment after CR; subjects who are relapsed after 12 months but have no response to the conventional chemotherapy; subjects who are relapsed twice or more; subjects who have persistent extramedullary leukemia.
- Subjects who are positive in CD33 or CLL1 test (according to the results of the central laboratory);
Show all 17Show fewer
- Subjects are allowed to have received ≤1 autologous HSCT;
- Subjects whose performance status scores of the Eastern Cooperative Oncology Organization (ECOG) are≤2;
- Subjects with the expected survival phase>3 months;
- Organ function should meet the following criteria:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN), unless these are caused by leukemia cell infiltration as determined by the investigator;
- Total serum bilirubin ≤ 1.5 times the upper limit of normal (ULN);
- Glomerular filtration rate (GFR)>50 mL/min;
- Left ventricular ejection fraction (LVEF)≥50%, no clinically significant pericardial effusion confirmed by echocardiography;
- Blood oxygen saturation under indoor ventilation in the screening phase>92%;
- Female subjects of childbearing age must be negative in the pregnancy test results in the screening phase;
- Male and female subjects of childbearing age must agree to take effective birth controls after signing the informed consent forms, during the study, and within 6 months after the last administration.
Who cannot join
- Subjects who are known to have acute promyelocytic leukemia;
- Subjects who suffer from or are suspected of suffering from central nervous system leukemia, or central nervous system involvement;
- Subjects who have received allogeneic HSCT;
- Subjects who have prior II-IV (Glucksberg criteria) acute graft versus-host disease (GvHD) or extensive chronic GvHD;
- Subjects who have received chimeric antigen receptor cell therapy or other cell therapy;
- Subjects who have received anti-tumor therapy in the early stage but are not recovered in the toxicity (according to NCI-CTCAE 5.0, the toxicity has not recovered to ≤ Grade 1, except for fatigue, anorexia, and alopecia);
Show all 23Show fewer
- Subjects who have had other malignant tumors within 5 years before inclusion, except for any type of carcinoma in situ that has been cured in the past and cured skin basal cell carcinoma or skin squamous cell carcinoma;
- Subjects whose cardiac function and disease meet one of the following conditions within 6 months before the first administration:
- Any risk factors that increase QTcF (Fridericia formula) interval prolongation, such as uncorrectable hypokalemia, hereditary long QT syndrome, and use of drugs that prolong the QTcF interval;
- New York Heart Association (NYHA) classification ≥Grade 3;
- QTcF interval prolongation (male>450 milliseconds; female>470 milliseconds);
- Unstable angina pectoris, and myocardial infarction;
- Subjects who have a history of autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.) that require systemic immunosuppressive/systemic disease modulating drugs within 2 years before the first administration;
- Subjects who have active systemic fungal, bacterial or viral infections that are uncontrolled or are required to be treated by intravenous administration;
- Subjects with human immunodeficiency virus (HIV) antibody positive;
- Subjects with HBsAg (-) and HBcAb (-). If subjects have HBsAg (+) and/or HBcAb (+), then subjects with HBV-DNA below the local lower limit of quantification can be included;
- Subjects with hepatitis C virus antibody (-). If subjects have hepatitis C virus antibody (+), then subjects with HCV-RNA (-) can be included;
- Female subjects who are breastfeeding and unwilling to stop breastfeeding;
- Subjects who have received major surgery (for the definition of major surgery, refer to the Level 3 and 4 surgeries specified in the Administrative Measures for the Clinical Application of Medical Technology) within 28 days before the first administration.
- Subjects who have received a solid organ transplant;
- Subjects who have a history of alcohol, drug use or drug abuse;
- Subjects who are known to be allergic to the study drug and/or main components and/or any excipients of the study drug;
- Subjects who have other severe, acute, or chronic diseases or laboratory abnormalities that may increase the risk of participating in the study and receiving the study drug, or may interfere with the interpretation of study results.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Wuxi People's Hospital
Wuxi, Jiangsu
Peihua Lu, MD, +8613583991399, lyzlyylxm@163.com
About this study
Official title: Clinical Study of Conjugated Antibody Redirecting Natural Killer (CAR-NK) Cells Targeting CD33 and CLL1 in Patients With Acute Myeloid Leukemia
This is an open-label, nonrandomized, investigator-initiated clinical trial to evaluate the safety, tolerability, pharmacokinetics, and efficacy of anti-CD33/CLL1 CAR-NK cell injection in patients with acute myeloid leukemia (AML), and to determine PK parameters, maximum tolerated dose (MTD), and phase II recommended dose (RP2D) for subjects receiving CAR-NK cell injection.
Read the detailed description
The treatment cycle in this study is 28 days. The administration of CAR-NK cells will be performed on day 1 and day 3 of each cycle. Subjects will be treated continuously until the criteria for termination of treatment are met. In this study, the dose escalation design is adopted. The first administration dose in the first cycle is 2.0×10^9 cells. If no adverse events were observed, the second administration dose in the first cycle would be 3.0×10^9 cells, and each administration dose in the second cycle and thereafter would be 3.0×10^9 cells.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Anti-CD33/CLL1 CAR-NK Cells
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CD33/CLL1 CAR-NK CellsBiological
The administration of CAR-NK cells will be performed on day 1 and day 3 of each cycle (28 days). The first administration dose in the first cycle is 2.0×10^9 cells. If no adverse events were observed, the second administration dose in the first cycle would be 3.0×10^9 cells, and each administration dose in the second cycle and thereafter would be 3.0×10^9 cells.
| Study group | Role | What they receive |
|---|---|---|
| Anti-CD33/CLL1 CAR-NK Cells | Experimental | The administration of CAR-NK cells will be performed on day 1 and day 3 of each cycle (28 days). The first administration dose in the first cycle is 2.0×10^9 cells. If no adverse events were observed, the second administration dose in the first cycle would be 3.0×10^9 cells, and each administration dose in the second cycle and thereafter would be 3.0×10^9 cells. Receives: Biological: Anti-CD33/CLL1 CAR-NK Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicity (DLT)
To evaluate the safety and tolerability of Anti-CD33/CLL1 CAR-NK cells
Measured: 28 days after initial infusion
Secondary outcomes (8)
Overall survival (OS)
To evaluate the effectivity of anti-CD33/CLL1 CAR-NK cells
Measured: Up to 1 year after infusion
Minimal residual disease (MRD)
To evaluate the effectivity of anti-CD33/CLL1 CAR-NK cells
Measured: Up to 1 year after infusion
Objective response rate (ORR)
To evaluate the effectivity of anti-CD33/CLL1 CAR-NK cells
Measured: Up to 1 year after infusion
Duration of overall response (DOR)
To evaluate the effectivity of anti-CD33/CLL1 CAR-NK cells
Measured: Up to 1 year after infusion
Plasma concentration of CAR-NK cells
Blood samples will be collected at specified time points to detect the number of CAR-NK cells in peripheral blood and to evaluate the PK parameters
Measured: One month after the last infusion
Cytokine release
Blood samples will be collected at specified time points to detect the cytokine (IL-6, TNF-α, IL-1ra, IL-10, IL-2, etc.) concentration (pg/mL)
Measured: One month after the last infusion
Adverse Events (AEs)
The incidence and severity of adverse events assessed according to Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, and the correlation between adverse events and CAR-NK cells
Measured: From day 1 to day 90 after the last infusion
Percentage of subjects receiving hematopoietic stem cell transplantation (HSCT)
To explore HSCT in subjects receiving CAR-NK cell therapy.
Measured: Up to 1 year after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2022
- Study start30 Nov 2020
- Primary completion30 Nov 2022 (estimated)
- Study completion30 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wuxi People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Imbioray (Hangzhou) Biomedicine Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05215015
- Sponsor's protocol ID
- IBR733-T01
- Other IDs
- WX-IBR-7
- Status last verified
- Jan 2022
- First submitted
- 18 Jan 2022
- Last updated
- 31 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of Conjugated Antibody Redirecting Natural Killer (CAR-NK) Cells Targeting CD33 and CLL1 in Patients With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05215015
- Acronym / sponsor ID
- IBR733-T01
- Conditions
- Acute Myeloid Leukemia
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Wuxi People's HospitalUniversity, hospital or other
- Collaborators
- Imbioray (Hangzhou) Biomedicine Co., Ltd.
- Study start
- 30 Nov 2020 (actual)
- Primary completion
- 30 Nov 2022 (estimated)
- Study completion
- 30 Nov 2022 (estimated)
- First posted
- 31 Jan 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 is an open-label, nonrandomized, investigator-initiated clinical trial to evaluate the safety, tolerability, pharmacokinetics, and efficacy of anti-CD33/CLL1 CAR-NK cell injection in patients with acute myeloid leukemia (AML), and to determine PK parameters, maximum tolerated dose (MTD), and phase II recommended dose (RP2D) for subjects receiving CAR-NK cell injection.
Detailed description
The treatment cycle in this study is 28 days. The administration of CAR-NK cells will be performed on day 1 and day 3 of each cycle. Subjects will be treated continuously until the criteria for termination of treatment are met. In this study, the dose escalation design is adopted. The first administration dose in the first cycle is 2.0×10^9 cells. If no adverse events were observed, the second administration dose in the first cycle would be 3.0×10^9 cells, and each administration dose in the second cycle and thereafter would be 3.0×10^9 cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-CD33/CLL1 CAR-NK Cells | Experimental | Biological: Anti-CD33/CLL1 CAR-NK CellsThe administration of CAR-NK cells will be performed on day 1 and day 3 of each cycle (28 days). The first administration dose in the first cycle is 2.0×10^9 cells. If no adverse events were observed, the second administration dose in the first cycle would be 3.0×10^9 cells, and each administration dose in the second cycle and thereafter would be 3.0×10^9 cells. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Subjects should voluntarily participate in this clinical study, are fully aware of the study, have signed the Informed Consent Forms, and are willing to follow and able to complete all trial procedures.
- Subjects who are more than 18 years old (including 18 years old), and less than 75 years old (including 75 years old);
- Subjects who are diagnosed as AML according to the World Health Organization (WHO) 2016 diagnosis criteria, and meet any of the following:
- Subjects who are positive in CD33 or CLL1 test (according to the results of the central laboratory);
- Subjects are allowed to have received ≤1 autologous HSCT;
Key exclusion criteria (23 listed)
- Subjects who are known to have acute promyelocytic leukemia;
- Subjects who suffer from or are suspected of suffering from central nervous system leukemia, or central nervous system involvement;
- Subjects who have received allogeneic HSCT;
- Subjects who have prior II-IV (Glucksberg criteria) acute graft versus-host disease (GvHD) or extensive chronic GvHD;
- Subjects who have received chimeric antigen receptor cell therapy or other cell therapy;
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 |
|---|---|---|
| Anti-CD33/CLL1 CAR-NK CellsThe administration of CAR-NK cells will be performed on day 1 and day 3 of each cycle (28 days). The first administration dose in the first cycle is 2.0×10^9 cells. If no adverse events were observed, the second administration dose in the first cycle would be 3.0×10^9 cells, and each administration dose in the second cycle and thereafter would be 3.0×10^9 cells. | Biological | Anti-CD33/CLL1 CAR-NK Cells |
Primary outcome
Incidence of dose limiting toxicity (DLT)
Time frame: 28 days after initial infusion
To evaluate the safety and tolerability of Anti-CD33/CLL1 CAR-NK cells
8 secondary outcomes
Overall survival (OS)
Time frame: Up to 1 year after infusion
Minimal residual disease (MRD)
Time frame: Up to 1 year after infusion
Objective response rate (ORR)
Time frame: Up to 1 year after infusion
Duration of overall response (DOR)
Time frame: Up to 1 year after infusion
Plasma concentration of CAR-NK cells
Time frame: One month after the last infusion
Cytokine release
Time frame: One month after the last infusion
Adverse Events (AEs)
Time frame: From day 1 to day 90 after the last infusion
Percentage of subjects receiving hematopoietic stem cell transplantation (HSCT)
Time frame: Up to 1 year after infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2022.
- Individual participant dataSharing planned: No
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Anti-CD33/CLL1 CAR-NK Cells in people with Acute Myeloid Leukemia, run by Wuxi People's Hospital 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 17 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 31 Jan 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xin Zhou, MD (+8613358111962, 13625653@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose limiting toxicity (DLT) (time frame: 28 days after initial infusion). 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 31 Jan 2022.