Description:
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.
Title
- Brief Title: Donor-derived Anti-CD123-CART Cells for Recurred AML After Allo-HSCT
- Official Title: Donor-derived Anti-CD123 Chimeric Antigen Receptors Modified T Cells for Recurred Acute Myeloid Leukaemia After Allogeneic Hematopoietic Stem Cell Transplantation
Clinical Trial IDs
- ORG STUDY ID:
307-RV-CAR-123
- NCT ID:
NCT03114670
Conditions
- Adult Acute Myeloid Leukemia
Interventions
Drug | Synonyms | Arms |
---|
CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells | anti-CD123 CART, CART123 | CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells | Experimental | Patients will receive a full dose CART infusion at day 0. | - CD123CAR-41BB-CD3zeta-EGFRt-expressing T cells
|
Eligibility Criteria
Inclusion Criteria:
1. Male and Female subjects with CD123+ acute myeloid leukemia as confirmed by
immunohistochemistry and flow cytometry;
2. 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.
3. Karnofsky score greater than 70%;
4. patients more than 18 years of age
5. Expected survival time >16 weeks;
6. Bilirubin <3.0 mg/dL,
7. Alanine aminotransferase(ALT)/ aspartate aminotransferase(AST)<3 fold normal.
8. Diffusing capacity of the lung for carbon monoxide(DLCO) and forced expiratory volume
in one second(FEV1)>45% of predictive value.
9. At least received three kinds of medicines functioning by different mechanisms,
including alkylating agents, protease inhibitors, and immunomodulators, and disease
progressing within 60 days.
10. Important organs are well tolerated;
11. For post-transplantation patients, the apheresis would be undertaken only at least 2
weeks after immunosuppressive agents for GvHD withdrawal;
12. From very beginning of the test to 30 days after the withdrawal, men and women should
adopt reliable contraceptive measures.
13. All research participants must have the ability to understand and willingness to sign
a written informed consent.
Exclusion criteria:
1. Patients were diagnosed with APL M3:t(15; 17)(q22; q12);PML/RARα );
2. Symptomatic active central nervous system leukaemia;
3. Patients with HIV, hepatitis B or C infection;
4. Any concurrent active malignancies;
5. Other uncontrolled active illness that hinders participation in the trial;
6. Patients suffer from coronary heart disease, angina pectoris, myocardial infarction,
arrhythmia, cerebral thrombosis, cerebral hemorrhage and other serious heart,
cerebrovascular disease;
7. patients with poorly controlled hypertensive
8. patients with froward psychiatric history
9. anyone who the researchers think unsuitable to participate in the investigation;
10. anyone who long-term use of immunosuppressive agents for organ transplants or other
reasons, or undertake inhaled corticosteroids therapy recently.
11. failed production release testing: CAR+ T cells <30% or T cell expansion less than
5-fold under the CD3/28 beads stimulation.
12. Pregnant, lactating or female patients planning to get pregnant within 2 months before
treatment ends;
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of adverse events related to treatment as assessed by NCI CTCAE version 4.03 |
Time Frame: | 15 years |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | CART cells persistence in vivo |
Time Frame: | 15 years |
Safety Issue: | |
Description: | |
Measure: | CAR123-specific antibody level |
Time Frame: | 15 years |
Safety Issue: | |
Description: | |
Measure: | Overall survival |
Time Frame: | 15 years |
Safety Issue: | |
Description: | |
Measure: | Disease response(CR, CRi) |
Time Frame: | 15 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Unknown status |
Lead Sponsor: | Affiliated Hospital to Academy of Military Medical Sciences |
Trial Keywords
- Leukemia
- Leukemia, Myeloid
- Recurrence
- Neoplasms by Histologic Type
- Disease Attributes
- Cyclophosphamide
- Fludarabine
- CD123
- Chimeric Antigen Receptor modified T-cells
Last Updated
June 14, 2017