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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Acute Leukemia, Acute Leukemia in Relapse, Acute Myeloid Leukemia, Relapsed or Refractory Acute Leukemia

Intervention / Treatment
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* Drug: anti-CD123 CAR-T treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Research patients enrolled are those patients with relapsed or refractory CD123+ acute leukemia (Acute Myeloid Leukemia/ acute lymphoblastic leukemia ); Relapsed: is defined as patients that had a first complete remission (CR) before developing recurrent disease (increased bone marrow blasts); 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; 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; Karnofsky performance status score >= 70; 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; 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; Serum bilirubin =< 3.0 mg/dL; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 times the institutional upper limits of normal; Ejection fraction measured by echocardiogram (ECHO) or multi gated acquisition scan (MUGA) >= 50%; Diffusion capacity of carbon monoxide (DLCO) or forced expiratory volume in one second (FEV1) > 45% predicted; Research participants' last dose of prior chemotherapy or radiation must be >= 2 weeks before leukapheresis; 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; Negative serum or urine pregnancy test; 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: Acute Promyelocytic Leukemia, t(15,17) (q22;q12); Pregnant and lactating women; Research participants who have tested human immunodeficiency virus (HIV) positive, or have active hepatitis B or C infection, or poorly controlled infection; History of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab Dependence on corticosteroids (5mg/day prednisone more than 2 weeks); A known hypersensitivity to any of the test materials or related compounds; Presence of active and clinically relevant Central Nervous System (CNS) disorder; Undergone prior allogeneic stem cell transplant, GVHD occurred within 6 months, requiring immunosuppressive therapy; Active autoimmune disease, such as psoriasis and rheumatoid arthritis; Other situations the clinicians think not eligible for participation in the research.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-CD123 CAR-T treatment<br> | Drug: anti-CD123 CAR-T treatment<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 | 28 days | 
| Incidence of adverse events | assessed by NCI CTCAE version 4.0 | Day 1-60 months after injection | 
| Disease response (CR or CRi) |  | Day 1-60 months after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | Day 1-60 months after injection | 
| Minimal residual disease |  | Day 1-60 months after injection |