Leukemia, Myeloid, AcutePhase 1NCT05008575
Anti-CD33 CAR NK Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
A Phase 1 study testing anti-CD33 CAR NK cells, Fludarabine and Cytoxan in people with Leukemia, Myeloid, Acute, run by Xinqiao Hospital of Chongqing at 1 site in China.
Trial summary
CAR technology has been used in T cell therapy and gets great success in treating hematological diseases. Following models of CAR T cells, CAR NK cell therapy has been one hot point. For myeloid malignancies, CD33 is widely expressed. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- anti-CD33 CAR NK cells, Fludarabine and Cytoxan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteChina
- Study dates
- 23 Dec 2021to 1 Dec 2023
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ECOG performance status score ≤ 2.
- Life expectancy ≥ 12 weeks from the time of enrollment.
- Disease status at the time of enrollment: -Patients with AML (except M3) who have not achieved complete remission after standard chemotherapy regimens; -Not suitable or unconditional for allogeneic hematopoietic stem cell transplantation; -Patients with recurrent acute myeloid leukemia after autologous hematopoietic stem cell transplantation without active graft-versus-host disease (GVHD).
- CD33 expression must be detected on greater than 50% of the malignant cells by immunohistochemistry or greater than 80% by flow cytometry.
- Adequate main organ function as assessed by the following laboratory requirements: creatinine ≤ 2.5 × upper limit of normal, cardiac ejection fraction ≥ 40%, oxygen saturation ≥ 90%, total bilirubin ≤ 3 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, Hgb≥80g/L.
- Without history of accepting anti-cancer therapy, including chemotherapy, radiotherapy, immunotherapy (immune suppressive drugs or corticosteroid treatment) within 4 weeks of screening.
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- Women of child-bearing age must have evidence of negative pregnancy test.
- Subjects of reproductive potential must agree to use acceptable birth control methods within 1 year after treatment, as described in protocol.
- After discussion by the expert group, the patient's condition was analyzed and combined with the general physical condition of the patient, the benefit of participating in the clinical trial was greater than the risk.
- All participants must have the ability to understand and willingness to sign a written informed consent.
Who cannot join
- Diagnosis of acute promyelocytic leukemia (APL M3): t(15;17)(q22;q12); (promyelocytic leukemia [PML]/retinoic acid receptor [RAR] alpha [a]) and variants excluded.
- Active acute or chronic GVHD or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
- Have been diagnosed with or treated other malignant tumors other than AML within 5 years before screening, except for the following conditions: participants with adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer; or received radical treatment Local prostate cancer, ductal carcinoma in situ.
- There are serious systemic diseases: New York Heart Association (NYHA) stage III or IV congestive heart failure; cerebrovascular accident or myocardial infarction or hemodynamic instability caused by arrhythmia within 6 months before signing the informed consent; impaired cardiac function (LVEF<50%) assessed by echocardiographic scan.
- Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
- Pregnant or lactating women.
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- Subjects with radiologically-detected CNS chloromas or CNS 3 disease (presence of ≥ 5/μL white blood cells (WBCs) in cerebral spinal fluid (CSF) and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia such as a cranial nerve palsy from active disease). Subjects with adequately treated CNS leukemia are eligible.
- Human immunodeficiency virus (HIV) seropositivity; hepatitis B surface antigen is positive or HBV DNA is higher than the detection limit of the analysis method; hepatitis C antibody is positive or HCV RNA is higher than the detection limit of the analysis method; syphilis antibody and syphilis rapid plasma reagin are positive; CMV DNA is positive.
- Patients who suffer from allergies for any cytokines or antibodies.
- Contraindications for fludarabine or cyclophosphamide treatment.
- Receiving corticosteroids at >20 mg daily prednisone dose or equivalent.
- Drug abuse and addiction.
- History of mental disorders.
- Other patients that researchers considered unsuitable for inclusion.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Hematology, Xinqiao Hospital
Chongqing, Chongqing Municipality, 400037
Xi Zhang, MD/PhD, 13808310064 ext. +86, zhangxxi@sina.com
Ruihao Huang, PhD candidate, 18984398751 ext. +86, 1169731117@qq.com
About this study
Official title: Phase I Study to Evaluate the Safety and Effectiveness of Anti-CD33 CAR NK Cell Therapy in Relapsed/Refractory Acute Myeloid Leukemia
CAR technology has been used in T cell therapy and gets great success in treating hematological diseases. Following models of CAR T cells, CAR NK cell therapy has been one hot point. For myeloid malignancies, CD33 is widely expressed. Targeting CD33 surface antigens by CAR NK cells provides an off-the-shelf immune cell therapy.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- anti-CD33 CAR NK cells, Fludarabine, Cytoxan
- 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 CAR NK cellsBiological
6×10^8, 12×10^8, 18×10^8/KG Treatment follows a lymphodepletion
FludarabineDrug
recommendation: 30mg/m2 (D-5~D-3),determined by tumor burden at baseline.
CytoxanDrug
recommendation: 300-500mg/m2 (D-5~D-3),determined by tumor burden at baseline.
| Study group | Role | What they receive |
|---|---|---|
| antiCD33 CAR NK cells | Experimental | After preconditioning with chemotherapy, the antiCD33 CAR NK cells will be evaluated Receives: Biological: anti-CD33 CAR NK cells; Drug: Fludarabine; Drug: Cytoxan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Remission Rate (ORR)
Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CRi), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies
Measured: 4 weeks after infusion
incidence of participants with dose limiting toxicity (DLT)
To characterize the safety, tolerability of Anti-CD33 CAR NK cells
Measured: within 4 weeks after infusion
Secondary outcomes (3)
Progression-free survival (PFS)
Measured: up to 2 years after infusion
Overall Response Rate (ORR)
Measured: up to 2 years after infusion
Overall survival(OS)
Measured: up to 2 years after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2021
- Study start23 Dec 2021
- Primary completion1 Dec 2022 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myeloid, AcuteStudies 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
- Model description
- Single Group Assignment
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xinqiao Hospital of Chongqing
- Sponsor type
- University, hospital or other
- Collaborators
- Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
- Responsible party
- Principal investigator, Xi Zhang, MD, Xinqiao Hospital of Chongqing
- Investigators
- xi zhang, MD/PhD, Principal investigator, Department of Hematology, Xinqiao Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05008575
- Sponsor's protocol ID
- CD33 CAR NK-AML
- Status last verified
- Dec 2021
- First submitted
- 14 Aug 2021
- Last updated
- 12 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huang R, Wang X, Yan H, Tan X, Ma Y, Wang M, Han X, Liu J, Gao L, Gao L, Jing G, Zhang C, Wen Q, Zhang X. Safety and efficacy of CD33-targeted CAR-NK cell therapy for relapsed/refractory AML: preclinical evaluation and phase I trial. Exp Hematol Oncol. 2025 Jan 2;14(1):1. doi: 10.1186/s40164-024-00592-6.
PubMed 39748428
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study to Evaluate the Safety and Effectiveness of Anti-CD33 CAR NK Cell Therapy in Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05008575
- Acronym / sponsor ID
- CD33 CAR NK-AML
- Conditions
- Leukemia, Myeloid, Acute
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Xinqiao Hospital of ChongqingUniversity, hospital or other
- Collaborators
- Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
- Study start
- 23 Dec 2021 (actual)
- Primary completion
- 1 Dec 2022 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 17 Aug 2021 (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.
CAR technology has been used in T cell therapy and gets great success in treating hematological diseases. Following models of CAR T cells, CAR NK cell therapy has been one hot point. For myeloid malignancies, CD33 is widely expressed. Targeting CD33 surface antigens by CAR NK cells provides an off-the-shelf immune cell therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Group Assignment
| Arm | Type | Receives |
|---|---|---|
| antiCD33 CAR NK cells | Experimental | Biological: anti-CD33 CAR NK cells, Drug: Fludarabine, Drug: CytoxanAfter preconditioning with chemotherapy, the antiCD33 CAR NK cells will be evaluated |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ECOG performance status score ≤ 2.
- Life expectancy ≥ 12 weeks from the time of enrollment.
- Disease status at the time of enrollment: -Patients with AML (except M3) who have not achieved complete remission after standard chemotherapy regimens; -Not suitable or unconditional for allogeneic hematopoietic stem cell transplantation; -Patients with recurrent acute myeloid leukemia after autologous hematopoietic stem cell transplantation without active graft-versus-host disease (GVHD).
- CD33 expression must be detected on greater than 50% of the malignant cells by immunohistochemistry or greater than 80% by flow cytometry.
- Adequate main organ function as assessed by the following laboratory requirements: creatinine ≤ 2.5 × upper limit of normal, cardiac ejection fraction ≥ 40%, oxygen saturation ≥ 90%, total bilirubin ≤ 3 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, Hgb≥80g/L.
Key exclusion criteria (14 listed)
- Diagnosis of acute promyelocytic leukemia (APL M3): t(15;17)(q22;q12); (promyelocytic leukemia [PML]/retinoic acid receptor [RAR] alpha [a]) and variants excluded.
- Active acute or chronic GVHD or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
- Have been diagnosed with or treated other malignant tumors other than AML within 5 years before screening, except for the following conditions: participants with adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer; or received radical treatment Local prostate cancer, ductal carcinoma in situ.
- There are serious systemic diseases: New York Heart Association (NYHA) stage III or IV congestive heart failure; cerebrovascular accident or myocardial infarction or hemodynamic instability caused by arrhythmia within 6 months before signing the informed consent; impaired cardiac function (LVEF<50%) assessed by echocardiographic scan.
- Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
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 CAR NK cells6×10^8, 12×10^8, 18×10^8/KG Treatment follows a lymphodepletion | Biological | antiCD33 CAR NK cells |
| Fludarabinerecommendation: 30mg/m2 (D-5~D-3),determined by tumor burden at baseline. | Drug | antiCD33 CAR NK cells |
| Cytoxanrecommendation: 300-500mg/m2 (D-5~D-3),determined by tumor burden at baseline. | Drug | antiCD33 CAR NK cells |
Primary outcome
Overall Remission Rate (ORR)
Time frame: 4 weeks after infusion
Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CRi), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies
incidence of participants with dose limiting toxicity (DLT)
Time frame: within 4 weeks after infusion
To characterize the safety, tolerability of Anti-CD33 CAR NK cells
3 secondary outcomes
Progression-free survival (PFS)
Time frame: up to 2 years after infusion
Overall Response Rate (ORR)
Time frame: up to 2 years after infusion
Overall survival(OS)
Time frame: up to 2 years after infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2022.
- Derived from this study: PubMed 39748428Huang R, Wang X, Yan H, Tan X, Ma Y, Wang M, Han X, Liu J, Gao L, Gao L, Jing G, Zhang C, Wen Q, Zhang X. Safety and efficacy of CD33-targeted CAR-NK cell therapy for relapsed/refractory AML: preclinical evaluation and phase I trial. Exp Hematol Oncol. 2025 Jan 2;14(1):1. doi: 10.1186/s40164-024-00592-6.
- Individual participant dataSharing planned: No
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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.
xi zhang, MD/PhD principal investigator
Department of Hematology, Xinqiao Hospital
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 anti-CD33 CAR NK cells, Fludarabine and Cytoxan in people with Leukemia, Myeloid, Acute, run by Xinqiao Hospital of Chongqing 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 10 inclusion and 14 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 12 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?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xi zhang, MD/PhD (13808310064 ext. +86, zhangxxi@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Remission Rate (ORR) (time frame: 4 weeks after infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05008575, which also lists 1 linked publication.
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 12 Jan 2022.