Donor-derived Anti-CD123-CART Cells for Recurred AML After Allo-HSCT
Study Details
Study Description
Brief 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. 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells Patients will receive a full dose CART infusion at day 0. |
Biological: CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells
a single dose of CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells will be infusion after preconditioning.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Incidence of adverse events related to treatment as assessed by NCI CTCAE version 4.03 [15 years]
Secondary Outcome Measures
- CART cells persistence in vivo [15 years]
- CAR123-specific antibody level [15 years]
- Overall survival [15 years]
- Disease response(CR, CRi) [15 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male and Female subjects with CD123+ acute myeloid leukemia as confirmed by immunohistochemistry and flow cytometry;
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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.
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Karnofsky score greater than 70%;
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patients more than 18 years of age
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Expected survival time >16 weeks;
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Bilirubin <3.0 mg/dL,
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Alanine aminotransferase(ALT)/ aspartate aminotransferase(AST)<3 fold normal.
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Diffusing capacity of the lung for carbon monoxide(DLCO) and forced expiratory volume in one second(FEV1)>45% of predictive value.
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At least received three kinds of medicines functioning by different mechanisms, including alkylating agents, protease inhibitors, and immunomodulators, and disease progressing within 60 days.
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Important organs are well tolerated;
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For post-transplantation patients, the apheresis would be undertaken only at least 2 weeks after immunosuppressive agents for GvHD withdrawal;
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From very beginning of the test to 30 days after the withdrawal, men and women should adopt reliable contraceptive measures.
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All research participants must have the ability to understand and willingness to sign a written informed consent.
Exclusion criteria:
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Patients were diagnosed with APL M3:t(15; 17)(q22; q12);PML/RARα ）；
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Symptomatic active central nervous system leukaemia;
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Patients with HIV, hepatitis B or C infection;
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Any concurrent active malignancies;
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Other uncontrolled active illness that hinders participation in the trial;
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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
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patients with froward psychiatric history
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anyone who the researchers think unsuitable to participate in the investigation;
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anyone who long-term use of immunosuppressive agents for organ transplants or other reasons, or undertake inhaled corticosteroids therapy recently.
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failed production release testing: CAR+ T cells <30% or T cell expansion less than 5-fold under the CD3/28 beads stimulation.
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Pregnant, lactating or female patients planning to get pregnant within 2 months before treatment ends;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fengtai District | Beijing Shi | China |
Sponsors and Collaborators
- Affiliated Hospital to Academy of Military Medical Sciences
Investigators
- Study Director: Hu Chen, M.D., Ph.D., Affiliated Hospital to Academy of Military Medical Sciences, China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 307-RV-CAR-123