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

• Status: Terminated
• Trial end date: 2019-07-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Second Affiliated Hospital of Xi'an Jiaotong University
• Collaborator: Nanjing Legend Biotech Co.

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.