Adult Acute Myeloid LeukemiaPhase 1NCT03114670
Donor-derived Anti-CD123-CART Cells for Recurred AML After Allo-HSCT
A Phase 1 study testing CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells in people with Adult Acute Myeloid Leukemia, run by Affiliated Hospital to Academy of Military Medical Sciences at 1 site in China.
Trial summary
Patients with acute myeloid leukemia(AML) recurred after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a dismal prognosis.The investigators developed donor-derived chimeric antigen receptor modified-T cell(CART) to target CD123 for the treatment of AML. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Myeloid Leukemia
- What is being tested?
- CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 25 Mar 2017to 18 Mar 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and Female subjects with CD123+ acute myeloid leukemia as confirmed by immunohistochemistry and flow cytometry;
- Patients must have received an allogenic stem cell transplantation(Allo-HSCT). The leukemia relapsed. There are available donor or enough cryopreserved donor-derived PBMCs for CART preparation and subsequent Allo-HSCT. In the previous case, the donor should have adequate venous access for apheresis.
- Karnofsky score greater than 70%;
- patients more than 18 years of age
- Expected survival time >16 weeks;
- Bilirubin <3.0 mg/dL,
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- Alanine aminotransferase(ALT)/ aspartate aminotransferase(AST)<3 fold normal.
- Diffusing capacity of the lung for carbon monoxide(DLCO) and forced expiratory volume in one second(FEV1)>45% of predictive value.
- At least received three kinds of medicines functioning by different mechanisms, including alkylating agents, protease inhibitors, and immunomodulators, and disease progressing within 60 days.
- Important organs are well tolerated;
- For post-transplantation patients, the apheresis would be undertaken only at least 2 weeks after immunosuppressive agents for GvHD withdrawal;
- From very beginning of the test to 30 days after the withdrawal, men and women should adopt reliable contraceptive measures.
- All research participants must have the ability to understand and willingness to sign a written informed consent.
Who cannot join
- Patients were diagnosed with APL M3:t(15; 17)(q22; q12);PML/RARα ）；
- Symptomatic active central nervous system leukaemia;
- Patients with HIV, hepatitis B or C infection;
- Any concurrent active malignancies;
- Other uncontrolled active illness that hinders participation in the trial;
- Patients suffer from coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage and other serious heart, cerebrovascular disease;
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- patients with poorly controlled hypertensive
- patients with froward psychiatric history
- anyone who the researchers think unsuitable to participate in the investigation;
- anyone who long-term use of immunosuppressive agents for organ transplants or other reasons, or undertake inhaled corticosteroids therapy recently.
- failed production release testing: CAR+ T cells <30% or T cell expansion less than 5-fold under the CD3/28 beads stimulation.
- Pregnant, lactating or female patients planning to get pregnant within 2 months before treatment ends;
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fengtai District
Beijing
Hu Chen, M.D., Ph.D., +86-010-6694-7108, chenhu217@aliyun.com
About this study
Official title: Donor-derived Anti-CD123 Chimeric Antigen Receptors Modified T Cells for Recurred Acute Myeloid Leukaemia After Allogeneic Hematopoietic Stem Cell Transplantation
Patients with acute myeloid leukemia(AML) recurred after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a dismal prognosis.The investigators developed donor-derived chimeric antigen receptor modified-T cell(CART) to target CD123 for the treatment of AML. The investigators start the Phase I study aimed to treat recurred post-transplantation AML patients using donor-derived CAR-T. The purpose of this study is to assess the safety and effectiveness of anti-CD123 CAR-T cells in patients.
Read the detailed description
Allo-HSCT is increasingly being used for AML, however, leukemia relapse remain a main problem for decades.Recently the investigators have witnessed great progresses in cancer therapy with chimeric antigen receptors modified T cells(CAR-T), especially for B-cell malignance. preclinical data about anti-CD123 CART have shown raised serious safety concerns of human anti-CD123 CAR-T for severe impairment of normal hematopoiesis in NSG mice.Patients with AML recurred after allo-HSCT have a dismal prognosis.The investigators developed donor-derived CART to target CD123 for the treatment of AML. The investigators start the Phase I study aimed to recurred post-transplantation AML patients using donor-derived CAR-T. The purpose of this study is to assess the safety and effectiveness of anti-CD123 CAR-T cells in patients.
- Conditions
- Adult Acute Myeloid Leukemia
- Being tested
- CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells
- Keywords
- Leukemia, Leukemia, Myeloid, Recurrence, Neoplasms by Histologic Type, Disease Attributes, Cyclophosphamide, Fludarabine, CD123, Chimeric Antigen Receptor modified T-cells
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Leukemia, Myeloid, Recurrence, Neoplasms by Histologic Type, Disease Attributes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD123CAR-41BB-CD3zeta-EGFRt-expressing T cellsBiological
Also called anti-CD123 CART, CART123
a single dose of CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells will be infusion after preconditioning.
| Study group | Role | What they receive |
|---|---|---|
| CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells | Experimental | Patients will receive a full dose CART infusion at day 0. Receives: Biological: CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events related to treatment as assessed by NCI CTCAE version 4.03
Measured: 15 years
Secondary outcomes (4)
CART cells persistence in vivo
Measured: 15 years
CAR123-specific antibody level
Measured: 15 years
Overall survival
Measured: 15 years
Disease response(CR, CRi)
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2017
- Study start25 Mar 2017
- Primary completion18 Mar 2019 (estimated)
- Study completion18 Mar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Affiliated Hospital to Academy of Military Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chen Hu, Affiliated Hospital to Academy of Military Medical Sciences
- Investigators
- Hu Chen, M.D., Ph.D., Study director, Affiliated Hospital to Academy of Military Medical Sciences, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03114670
- Sponsor's protocol ID
- 307-RV-CAR-123
- Status last verified
- Jun 2017
- First submitted
- 21 Mar 2017
- Last updated
- 14 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donor-derived Anti-CD123 Chimeric Antigen Receptors Modified T Cells for Recurred Acute Myeloid Leukaemia After Allogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03114670
- Acronym / sponsor ID
- 307-RV-CAR-123
- Conditions
- Adult Acute Myeloid Leukemia
- Keywords
- Leukemia, Leukemia, Myeloid, Recurrence, Neoplasms by Histologic Type, Disease Attributes, Cyclophosphamide, Fludarabine, CD123
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Affiliated Hospital to Academy of Military Medical SciencesUniversity, hospital or other
- Study start
- 25 Mar 2017 (actual)
- Primary completion
- 18 Mar 2019 (estimated)
- Study completion
- 18 Mar 2021 (estimated)
- First posted
- 14 Apr 2017 (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.
Patients with acute myeloid leukemia(AML) recurred after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a dismal prognosis.The investigators developed donor-derived chimeric antigen receptor modified-T cell(CART) to target CD123 for the treatment of AML. The investigators start the Phase I study aimed to treat recurred post-transplantation AML patients using donor-derived CAR-T. The purpose of this study is to assess the safety and effectiveness of anti-CD123 CAR-T cells in patients.
Detailed description
Allo-HSCT is increasingly being used for AML, however, leukemia relapse remain a main problem for decades.Recently the investigators have witnessed great progresses in cancer therapy with chimeric antigen receptors modified T cells(CAR-T), especially for B-cell malignance. preclinical data about anti-CD123 CART have shown raised serious safety concerns of human anti-CD123 CAR-T for severe impairment of normal hematopoiesis in NSG mice.Patients with AML recurred after allo-HSCT have a dismal prognosis.The investigators developed donor-derived CART to target CD123 for the treatment of AML. The investigators start the Phase I study aimed to recurred post-transplantation AML patients using donor-derived CAR-T. The purpose of this study is to assess the safety and effectiveness of anti-CD123 CAR-T cells in patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells | Experimental | Biological: CD123CAR-41BB-CD3zeta-EGFRt-expressing T cellsPatients will receive a full dose CART infusion at day 0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male and Female subjects with CD123+ acute myeloid leukemia as confirmed by immunohistochemistry and flow cytometry;
- Patients must have received an allogenic stem cell transplantation(Allo-HSCT). The leukemia relapsed. There are available donor or enough cryopreserved donor-derived PBMCs for CART preparation and subsequent Allo-HSCT. In the previous case, the donor should have adequate venous access for apheresis.
- Karnofsky score greater than 70%;
- patients more than 18 years of age
- Expected survival time >16 weeks;
Key exclusion criteria (12 listed)
- Patients were diagnosed with APL M3:t(15; 17)(q22; q12);PML/RARα ）；
- Symptomatic active central nervous system leukaemia;
- Patients with HIV, hepatitis B or C infection;
- Any concurrent active malignancies;
- Other uncontrolled active illness that hinders participation in the trial;
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 |
|---|---|---|
| CD123CAR-41BB-CD3zeta-EGFRt-expressing T cellsAlso: anti-CD123 CART, CART123a single dose of CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells will be infusion after preconditioning. | Biological | CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells |
Primary outcome
Incidence of adverse events related to treatment as assessed by NCI CTCAE version 4.03
Time frame: 15 years
4 secondary outcomes
CART cells persistence in vivo
Time frame: 15 years
CAR123-specific antibody level
Time frame: 15 years
Overall survival
Time frame: 15 years
Disease response(CR, CRi)
Time frame: 15 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
- Individual participant dataSharing planned: Undecided
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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.
Hu Chen, M.D., Ph.D. study director
Affiliated Hospital to Academy of Military Medical Sciences, China
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 CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells in people with Adult Acute Myeloid Leukemia, run by Affiliated Hospital to Academy of Military Medical Sciences 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 13 inclusion and 12 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 14 Jun 2017. 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 Hu Chen, M.D., Ph.D. (+86-010-6694-7108, chenhu217@aliyun.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events related to treatment as assessed by NCI CTCAE version 4.03 (time frame: 15 years). 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 14 Jun 2017.