Leukemia, Myeloid, AcuteEarly Phase 1NCT05016063
Dual CD33-CLL1-CAR-T Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
A Early Phase 1 study testing Fludarabine, Cytoxan and Dual CD33-CLL1 CAR-T cells in people with Leukemia, Myeloid, Acute, run by Xinqiao Hospital of Chongqing at 1 site in China.
Trial summary
Phase I, interventional, single-arm, open-label, treatment study to evaluate the safety and effectiveness of CD33-CLL1 CAR in patients with relapsed and/or refractory acute myeloid leukemia (AML). 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?
- Fludarabine, Cytoxan and Dual CD33-CLL1 CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2021to 1 Sep 2023
- 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 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
Department of Hematology, Xinqiao Hospital
Chongqing, Chongqing Municipality, 400037
About this study
Official title: Phase I Study to Evaluate the Safety and Effectiveness of Dual CD33-CLL1 CAR-T Therapy in Relapsed/Refractory Acute Myeloid Leukemia
Phase I, interventional, single-arm, open-label, treatment study to evaluate the safety and effectiveness of CD33-CLL1 CAR in patients with relapsed and/or refractory acute myeloid leukemia (AML).
Read the detailed description
AML bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CLL1 expression comprise a rare population that also plays an important role in disease progression and relapse for myeloid malignancies. CD33 is widely expressed in AML. Targeting both CD33 and CLL1 surface antigens together may offer two distinct benefits. First, targeting both bulk disease and leukemic stem cells together allows for a more comprehensive ablation of the disease. Second, dual targeting of myeloid malignancies by both CD33 and CLL1 directed therapy overcomes the pitfalls of single-antigen therapy by preventing relapse due to antigen loss. While loss of a single antigen under antigen-specific selection pressure is possible, loss of two antigens simultaneously is much less likely.
CD33-CLL1 CAR is a compound Chimeric Antigen Receptor immunotherapy with two distinct functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1 and CD33. CD33-CLL1 CAR intends to target the mechanisms of single-CAR relapse, specifically antigen escape and leukemic stem cells.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- Fludarabine, Cytoxan, Dual CD33-CLL1 CAR-T 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.
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.
Dual CD33-CLL1 CAR-T cellsBiological
CD33-CLL1 CAR-T infusion (starting at dose level 1 [DL1]: 0.5 x 106 transduced CAR-T cells/kg) on Day 0.
| Study group | Role | What they receive |
|---|---|---|
| Dual CD33-CLL1 CAR-T cells | Experimental | CD33-CLL1 CAR T cells Receives: Drug: Fludarabine; Drug: Cytoxan; Biological: Dual CD33-CLL1 CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response 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
the safety evaluation of Dual CD33-CLL1 CAR-T cells
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: within 4 weeks after infusion
Secondary outcomes (2)
Progression-free survival (PFS)
Surviavl without disease progression
Measured: up to 2 years after infusion
Overall survival(OS)
Surviavl
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 posted23 Aug 2021
- Study start1 Sep 2021 (estimated)
- Primary completion1 Sep 2022 (estimated)
- Study completion1 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 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, PhD/MD, Principal investigator, Department of Hematology, Xinqiao Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05016063
- Sponsor's protocol ID
- Dual CD33-CLL1 CAR-T cells
- Status last verified
- Aug 2021
- First submitted
- 14 Aug 2021
- Last updated
- 23 Aug 2021
- 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 23 Aug 2021. 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 Dual CD33-CLL1 CAR-T Therapy in Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05016063
- Acronym / sponsor ID
- Dual CD33-CLL1 CAR-T cells
- Conditions
- Leukemia, Myeloid, Acute
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Xinqiao Hospital of ChongqingUniversity, hospital or other
- Collaborators
- Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
- Study start
- 1 Sep 2021 (estimated)
- Primary completion
- 1 Sep 2022 (estimated)
- Study completion
- 1 Sep 2023 (estimated)
- First posted
- 23 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.
Phase I, interventional, single-arm, open-label, treatment study to evaluate the safety and effectiveness of CD33-CLL1 CAR in patients with relapsed and/or refractory acute myeloid leukemia (AML).
Detailed description
AML bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CLL1 expression comprise a rare population that also plays an important role in disease progression and relapse for myeloid malignancies. CD33 is widely expressed in AML. Targeting both CD33 and CLL1 surface antigens together may offer two distinct benefits. First, targeting both bulk disease and leukemic stem cells together allows for a more comprehensive ablation of the disease. Second, dual targeting of myeloid malignancies by both CD33 and CLL1 directed therapy overcomes the pitfalls of single-antigen therapy by preventing relapse due to antigen loss. While loss of a single antigen under antigen-specific selection pressure is possible, loss of two antigens simultaneously is much less likely.
CD33-CLL1 CAR is a compound Chimeric Antigen Receptor immunotherapy with two distinct functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1 and CD33. CD33-CLL1 CAR intends to target the mechanisms of single-CAR relapse, specifically antigen escape and leukemic stem cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dual CD33-CLL1 CAR-T cells | Experimental | Drug: Fludarabine, Drug: Cytoxan, Biological: Dual CD33-CLL1 CAR-T cellsCD33-CLL1 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 (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 |
|---|---|---|
| Fludarabinerecommendation: 30mg/m2 (D-5~D-3),determined by tumor burden at baseline. | Drug | Dual CD33-CLL1 CAR-T cells |
| Cytoxanrecommendation: 300-500mg/m2 (D-5~D-3),determined by tumor burden at baseline. | Drug | Dual CD33-CLL1 CAR-T cells |
| Dual CD33-CLL1 CAR-T cellsCD33-CLL1 CAR-T infusion (starting at dose level 1 [DL1]: 0.5 x 106 transduced CAR-T cells/kg) on Day 0. | Biological | Dual CD33-CLL1 CAR-T cells |
Primary outcome
Overall Response 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
the safety evaluation of Dual CD33-CLL1 CAR-T cells
Time frame: within 4 weeks after infusion
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
2 secondary outcomes
Progression-free survival (PFS)
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 23 Aug 2021.
- 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, PhD/MD 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 Early Phase 1 study testing Fludarabine, Cytoxan and Dual CD33-CLL1 CAR-T cells 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 23 Aug 2021. 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 xi zhang, PhD/MD (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 Response 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?
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 23 Aug 2021.