Study Evaluating Safety and Efficacy of CAR-T Cells Targeting CD123 in Patients With Acute Leukemia
Study Evaluating Safety and Efficacy of CAR-T Cells Targeting CD123 in Patients With Acute Leukemia
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.
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.
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.