study evaluating safety and efficacy of car-t cells targeting cd123 in patients with acute leukemia

Conditions: Acute Leukemia; Acute Leukemia in Relapse; Acute Myeloid Leukemia; Relapsed or Refractory Acute Leukemia

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.

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.

Eligibility criteria:
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.