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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03672851
• Other study ID #: anti-CD123 CAR-T therapy
• Status: Terminated
• Phase: Phase 1
• Start date: April 17, 2019
• Est. completion date: July 31, 2019

Study information

• Verified date: May 2019
• Source: Second Affiliated Hospital of Xi'an Jiaotong University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: July 31, 2019
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemia
• Acute Leukemia in Relapse
• Acute Myeloid Leukemia
• Leukemia
• Relapsed or Refractory Acute Leukemia

Intervention

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.

Locations

Country	Name	City	State
China	Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi

Sponsors (2)

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	28 days
Primary	Incidence of adverse events	assessed by NCI CTCAE version 4.0	Day 1-60 months after injection
Primary	Disease response (CR or CRi)		Day 1-60 months after injection
Secondary	Survival		Day 1-60 months after injection
Secondary	Minimal residual disease		Day 1-60 months after injection