Acute Leukemia, Acute Leukemia in Relapse, Acute Myeloid Leukemia, Relapsed or Refractory Acute Leukemia
Conditions
Brief summary
This is a single arm, open-label, phase 1 study, to determine the safety and efficacy of anti-CD123 CAR-T cells in treating patients diagnosed with refractory/relapsed acute leukemia in a dose-escalation way.
Detailed description
This is a dose-escalation study of autologous anti-CD123 CAR-T cells. Patients receive fludarabine phosphate(300 mg/m\^2) and cyclophosphamide (30 mg/m\^2) IV on days -5 to -3, and then Patients receive autologous anti-CD123 CAR T cells IV over 20 minutes on day 0 (20% of total dose), day2 (30% of total dose) and day6 (50% of total dose, according to the side-effects occured). The total dose of CAR-T cells used in dose-escalation study is 0.5x10\^6- 2.0x10\^6 CAR-T cells/kg.
Interventions
DRUGanti-CD123 CAR-T treatment
Patients receive fludarabine phosphate(300 mg/m\^2) and cyclophosphamide (30 mg/m\^2) IV on days -5 to -3, and then Patients receive autologous anti-CD123 CAR T cells IV over 20 minutes on day 0 (20% of total dose), day2 (30% of total dose) and day6 (50% of total dose, according to the side-effects occured). The total dose of CAR-T cells used in dose-escalation study is 0.5x10\^6- 2.0x10\^6 CAR-T cells/kg.
Sponsors
Nanjing Legend Biotech Co.
Second Affiliated Hospital of Xi'an Jiaotong University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Research patients enrolled are those patients with relapsed or refractory CD123+ acute leukemia (Acute Myeloid Leukemia/ acute lymphoblastic leukemia ); 2. Relapsed: is defined as patients that had a first complete remission (CR) before developing recurrent disease (increased bone marrow blasts); 3. Refractory: is defined as patients that have not achieved a first CR after 2 cycles of induction chemotherapy; for patients with leukemia evolving from myelodysplastic syndrome, they should have completed at least one cycle of induction chemotherapy; 4. Research participants must have bone marrow and/or peripheral blood samples available for confirmation of diagnosis; CD123 positivity must be confirmed by either flow cytometry or immunohistochemistry within 90 days of study entry; cytogenetics, flow cytometry, and molecular studies (such as FMS-like tyrosine kinase-3 \[FLT-3\] status) will be obtained as per standard practice; 5. Karnofsky performance status score \>= 70; 6. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately; 7. Calculated creatinine clearance (absolute value) of \>= 50 mL/minute or creatinine \< 2.0 mg/dl or \< 2 times upper limit of normal for the research participant's age group; 8. Serum bilirubin =\< 3.0 mg/dL; 9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 5 times the institutional upper limits of normal; 10. Ejection fraction measured by echocardiogram (ECHO) or multi gated acquisition scan (MUGA) \>= 50%; 11. Diffusion capacity of carbon monoxide (DLCO) or forced expiratory volume in one second (FEV1) \> 45% predicted; 12. Research participants' last dose of prior chemotherapy or radiation must be \>= 2 weeks before leukapheresis; 13. If a research participant has undergone prior allogeneic stem cell transplant, he/she must be off all immunosuppressants for graft versus host disease (GVHD) for at least 2 weeks before undergoing leukapheresis; 14. Negative serum or urine pregnancy test; 15. All research participants must have the ability to understand and willingness to sign a written informed consent or age appropriate assent for pediatric patients.
Exclusion criteria
1. Acute Promyelocytic Leukemia, t(15,17) (q22;q12); 2. Pregnant and lactating women; 3. Research participants who have tested human immunodeficiency virus (HIV) positive, or have active hepatitis B or C infection, or poorly controlled infection; 4. History of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab 5. Dependence on corticosteroids (5mg/day prednisone more than 2 weeks); 6. A known hypersensitivity to any of the test materials or related compounds; 7. Presence of active and clinically relevant Central Nervous System (CNS) disorder; 8. Undergone prior allogeneic stem cell transplant, GVHD occurred within 6 months, requiring immunosuppressive therapy; 9. Active autoimmune disease, such as psoriasis and rheumatoid arthritis; 10. Other situations the clinicians think not eligible for participation in the research.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | 28 days | assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Incidence of adverse events | Day 1-60 months after injection | assessed by NCI CTCAE version 4.0 |
| Disease response (CR or CRi) | Day 1-60 months after injection | — |
Secondary
| Measure | Time frame |
|---|---|
| Survival | Day 1-60 months after injection |
| Minimal residual disease | Day 1-60 months after injection |
Countries
China
Outcome results
None listed