Acute Myeloid Leukemia RefractoryPhase 1/2NCT06125652
Administration of Anti Tim-3/CD123 CAR-T Cell Therapy in Relapsed and Refractory Acute Myeloid Leukemia (rr/AML)
A Phase 1/2 study testing anti Tim-3/CD123 CAR-T cell therapy in people with Acute Myeloid Leukemia Refractory and Acute Myeloid Leukemia, in Relapse, run by Xuzhou Medical University at 1 site in China.
Trial summary
To evaluate the safety and efficacy of anti Tim3/CD123 CAR-T cells in the treatment of relapsed and refractory acute myeloid leukemia. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia Refractory, Acute Myeloid Leukemia, in Relapse
- What is being tested?
- anti Tim-3/CD123 CAR-T cell therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 4 Nov 2023to 1 Jan 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- All subjects must sign and date the Informed Consent before initiating any study specific procedures or activities;
- At the age of 18-70 years old;
- Diagnosed as relapse/refractory (r/r) de novo or secondary acute myeloid leukemia (AML);
- The patient has recovered from the toxicity of previous treatment;
- ECOG score ≤ 2 and expected survival period is not less than 3 months;
- Adequate organ function defined as:AST ≤3×ULN; ALT ≤3×ULN; Total bilirubin ≤1.5×ULN; Serum creatinine ≤1.5×ULN, or CCR≥60 mL/min; Hemoglobin ≥60g/L ; Indoor oxygen saturation ≥92%; LVEF≥45%;
- Pregnancy testing: females of childbearing potential must have a negative serum or urine pregnancy test;
- From the use of study drug to 2 years after treatment, males and female of childbearing potential must agree to use an effective method of contraception.
Who cannot join
- Diagnosis of acute promyelocytic leukemia;
- History or presence of a CNS disorder;
- HBsAg is positive; HCV #HIV or Syphilis antibody are positive, CMV-DNA in peripheral blood is more than≥500 copies /mL;
- History of severe hypersensitivity reaction;
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, atrial fibrillation, or other clinically significant cardiac disease within 12 months before enrollment;
- History of organ transplant surgery;
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- Required systemic application of immunosuppressive or other drugs;
- Auto-SCT within the 3 months before enrollment;
- Active autoimmune or inflammatory diseases of the nervous system (e.g., Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES));
- Requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, leukostasis or tumor lysis syndrome (TLS)) ;
- Presence or suspicion of a fungal, bacterial, viral, or other infection that is uncontrolled or requiring antimicrobials for management;
- Live vaccine received within the ≤ 4 weeks before enrollment;
- Persons with serious mental illness;
- History of major surgical operations four weeks before enrollment;
- History of alcoholism or substance abuse;
- Was identified by the investigators as unsuitable to participate in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Kailin Xu
Xuzhou, Jiangsu, 221000
Kailin Xu, M.D., Ph.D., 15162166166, lihmd@163.com
About this study
Official title: Application of Anti Tim-3/CD123 CAR-T Cell Therapy in Relapsed and Refractory Acute Myeloid Leukemia (rr/AML)
To evaluate the safety and efficacy of anti Tim3/CD123 CAR-T cells in the treatment of relapsed and refractory acute myeloid leukemia.
Read the detailed description
Cluster of Differentiation 123 (CD123) is usually overexpressed on leukemia stem cells (LSCs) in acute myeloid leukemia (AML). However, CD123 has poor specificity and is also expressed on normal hematopoietic stem cells (HSC), myeloid cells, and some non-hematopoietic cells. This leads to widespread on-target off-tumor effect in the clinical application of anti CD123 CAR-T cells, manifested as severe bone marrow suppression, organ damage, and patients experiencing infections, bleeding, and organ dysfunction. T cell immunoglobulin and mucin domain 3 (Tim-3) belongs to the Tim gene family. 85% of LSCs highly express Tim-3, while normal hematopoietic stem/progenitor cells (HSC/P), granulocytes, and macrophages do not express Tim-3. Compared with CD123, seeing Tim-3 as a recognition tool for LSCs has higher specificity. In vivo and in vitro studies have confirmed that anti Tim-3 CAR-T cells have significant anti LSCs effects, while not affecting the ability of normal HSC/P to form colonies and differentiate lineages. We believe that using both Tim-3 and CD123 as targets for CAR-T cells can improve the specificity of recognizing LSCs, reduce the killing effect of CAR-T cells on HSC/P expressing CD123, and thus reduce the on-target off-tumor effect.
- Being tested
- anti Tim-3/CD123 CAR-T cell therapy
- 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 Tim-3/CD123 CAR-T cell therapyDrug
Enrolled patients will receive prespecified dose of autologous CAR-T cells.
| Study group | Role | What they receive |
|---|---|---|
| anti Tim-3/CD123 CAR-T cell therapy | Experimental | Enrolled patients will receive prespecified dose of autologous CAR-T cells. Receives: Drug: anti Tim-3/CD123 CAR-T cell therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity #DLT#
Adverse events assessed according to NCI-CTCAE v5.0
Measured: Baseline up to 28 days after CAR-T cells infusion
Secondary outcomes (4)
MRD negative overall response rate (MRD- ORR)
Assessment of MRD negative overall response rate (MRD- ORR) at 3 months of treatment
Measured: 3 months
Overall response rate (ORR)
Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24
Measured: Month 6, 12, 18 and 24
Event-free survival (EFS)
Assessment of EFS at Month 6, 12, 18 and 24
Measured: Month 6, 12, 18 and 24
Overall survival (OS)
Assessment of OS at Month 6, 12, 18 and 24
Measured: Month 6, 12, 18 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2023
- Study start4 Nov 2023
- Primary completion1 Jan 2026 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia RefractoryStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuzhou Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kai Lin Xu，MD, Xuzhou Medical University
- Investigators
- Kailin Xu, MD.,PD., Study chair, The Affiliated Hospital oh Xuzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06125652
- Sponsor's protocol ID
- XYFY2023-KL358-01
- Status last verified
- Nov 2023
- First submitted
- 4 Nov 2023
- Last updated
- 9 Nov 2023
- 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 9 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of Anti Tim-3/CD123 CAR-T Cell Therapy in Relapsed and Refractory Acute Myeloid Leukemia (rr/AML)
- ClinicalTrials.gov ID
- NCT06125652
- Acronym / sponsor ID
- XYFY2023-KL358-01
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Xuzhou Medical UniversityUniversity, hospital or other
- Study start
- 4 Nov 2023 (actual)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 9 Nov 2023 (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.
To evaluate the safety and efficacy of anti Tim3/CD123 CAR-T cells in the treatment of relapsed and refractory acute myeloid leukemia.
Detailed description
Cluster of Differentiation 123 (CD123) is usually overexpressed on leukemia stem cells (LSCs) in acute myeloid leukemia (AML). However, CD123 has poor specificity and is also expressed on normal hematopoietic stem cells (HSC), myeloid cells, and some non-hematopoietic cells. This leads to widespread on-target off-tumor effect in the clinical application of anti CD123 CAR-T cells, manifested as severe bone marrow suppression, organ damage, and patients experiencing infections, bleeding, and organ dysfunction. T cell immunoglobulin and mucin domain 3 (Tim-3) belongs to the Tim gene family. 85% of LSCs highly express Tim-3, while normal hematopoietic stem/progenitor cells (HSC/P), granulocytes, and macrophages do not express Tim-3. Compared with CD123, seeing Tim-3 as a recognition tool for LSCs has higher specificity. In vivo and in vitro studies have confirmed that anti Tim-3 CAR-T cells have significant anti LSCs effects, while not affecting the ability of normal HSC/P to form colonies and differentiate lineages. We believe that using both Tim-3 and CD123 as targets for CAR-T cells can improve the specificity of recognizing LSCs, reduce the killing effect of CAR-T cells on HSC/P expressing CD123, and thus reduce the on-target off-tumor effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| anti Tim-3/CD123 CAR-T cell therapy | Experimental | Drug: anti Tim-3/CD123 CAR-T cell therapyEnrolled patients will receive prespecified dose of autologous CAR-T cells. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- All subjects must sign and date the Informed Consent before initiating any study specific procedures or activities;
- At the age of 18-70 years old;
- Diagnosed as relapse/refractory (r/r) de novo or secondary acute myeloid leukemia (AML);
- The patient has recovered from the toxicity of previous treatment;
- ECOG score ≤ 2 and expected survival period is not less than 3 months;
Key exclusion criteria (16 listed)
- Diagnosis of acute promyelocytic leukemia;
- History or presence of a CNS disorder;
- HBsAg is positive; HCV #HIV or Syphilis antibody are positive, CMV-DNA in peripheral blood is more than≥500 copies /mL;
- History of severe hypersensitivity reaction;
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, atrial fibrillation, or other clinically significant cardiac disease within 12 months before enrollment;
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 Tim-3/CD123 CAR-T cell therapyEnrolled patients will receive prespecified dose of autologous CAR-T cells. | Drug | anti Tim-3/CD123 CAR-T cell therapy |
Primary outcome
Dose-limiting toxicity #DLT#
Time frame: Baseline up to 28 days after CAR-T cells infusion
Adverse events assessed according to NCI-CTCAE v5.0
4 secondary outcomes
MRD negative overall response rate (MRD- ORR)
Time frame: 3 months
Overall response rate (ORR)
Time frame: Month 6, 12, 18 and 24
Event-free survival (EFS)
Time frame: Month 6, 12, 18 and 24
Overall survival (OS)
Time frame: Month 6, 12, 18 and 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2023.
- 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.
Kailin Xu, MD.,PD. study chair
The Affiliated Hospital oh Xuzhou Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing anti Tim-3/CD123 CAR-T cell therapy in people with Acute Myeloid Leukemia Refractory and Acute Myeloid Leukemia, in Relapse, run by Xuzhou Medical University 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 8 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 9 Nov 2023. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kailin Xu, MD.,PD. (15162166166, lihmd@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity #DLT# (time frame: Baseline up to 28 days after CAR-T cells 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 9 Nov 2023.