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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Acute Leukemia; Acute Leukemia in Relapse; Relapsed or Refractory Acute Leukemia
• Intervention / Treatment: Drug: anti-CD123 CAR-T treatment

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710000
      • Second Affiliated Hospital of Xi'an JiaoTong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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	Time Frame
Survival	Day 1-60 months after injection
Minimal residual disease	Day 1-60 months after injection

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Xi'an Jiaotong University
• Collaborators: Nanjing Legend Biotech Co.
• Investigators: Principal Investigator: Ai-Li He, MD, PhD, Second Affiliated Hospital of Xi'an JiaoTong University

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 17, 2019
• Primary Completion (ACTUAL): July 31, 2019
• Study Completion (ACTUAL): July 31, 2019

Study Registration Dates

• First Submitted: September 13, 2018
• First Submitted That Met QC Criteria: September 13, 2018
• First Posted (ACTUAL): September 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2019
• Last Update Submitted That Met QC Criteria: September 3, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Acute Disease
• Other Study ID Numbers: anti-CD123 CAR-T therapy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No