Study Evaluating Safety and Efficacy of CAR-T Cells Targeting CD123 in Patients With Acute Leukemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is a dose-escalation study of autologous anti-CD123 CAR-T cells. Patients receive fludarabine phosphate(300 mg/m2) and cyclophosphamide (30 mg/m2) 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 0.5x106- 2.0x106 CAR-T cells/kg.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: anti-CD123 CAR-T treatment
|
Drug: anti-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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Survival [Day 1-60 months after injection]
- Minimal residual disease [Day 1-60 months after injection]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Research patients enrolled are those patients with relapsed or refractory CD123+ acute leukemia (Acute Myeloid Leukemia/ acute lymphoblastic leukemia );
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Relapsed: is defined as patients that had a first complete remission (CR) before developing recurrent disease (increased bone marrow blasts);
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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;
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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;
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Karnofsky performance status score >= 70;
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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;
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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;
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Serum bilirubin =< 3.0 mg/dL;
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Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 times the institutional upper limits of normal;
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Ejection fraction measured by echocardiogram (ECHO) or multi gated acquisition scan (MUGA) >= 50%;
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Diffusion capacity of carbon monoxide (DLCO) or forced expiratory volume in one second (FEV1) > 45% predicted;
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Research participants' last dose of prior chemotherapy or radiation must be >= 2 weeks before leukapheresis;
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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;
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Negative serum or urine pregnancy test;
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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:
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Acute Promyelocytic Leukemia, t(15,17) (q22;q12);
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Pregnant and lactating women;
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Research participants who have tested human immunodeficiency virus (HIV) positive, or have active hepatitis B or C infection, or poorly controlled infection;
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History of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab
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Dependence on corticosteroids (5mg/day prednisone more than 2 weeks);
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A known hypersensitivity to any of the test materials or related compounds;
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Presence of active and clinically relevant Central Nervous System (CNS) disorder;
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Undergone prior allogeneic stem cell transplant, GVHD occurred within 6 months, requiring immunosuppressive therapy;
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Active autoimmune disease, such as psoriasis and rheumatoid arthritis;
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Other situations the clinicians think not eligible for participation in the research.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Second Affiliated Hospital of Xi'an Jiaotong University | Xi'an | Shaanxi | China | 710000 |
Sponsors and Collaborators
- Second Affiliated Hospital of Xi'an Jiaotong University
- Nanjing Legend Biotech Co.
Investigators
- Principal Investigator: Ai-Li He, MD, PhD, Second Affiliated Hospital of Xi'an Jiaotong University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- anti-CD123 CAR-T therapy