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

NCT03672851 | Terminated Phase 1

• 1 other identifier: anti-CD123 CAR-T therapy
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Leukemia; Acute Leukemia in Relapse; Acute Myeloid Leukemia; Relapsed or Refractory Acute Leukemia

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Survival

  Day 1-60 months after injection

• Minimal residual disease

  Day 1-60 months after injection

Study Arms (1)

anti-CD123 CAR-T treatment

EXPERIMENTAL

Drug: anti-CD123 CAR-T treatment

Interventions

anti-CD123 CAR-T treatment DRUG

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.

anti-CD123 CAR-T treatment

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital of Xi'an Jiaotong University: lead
• Nanjing Legend Biotech Co.: collaborator

Study Sites (1)

Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ai-Li He, MD, PhD

  Second Affiliated Hospital of Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2018
• First Posted: September 17, 2018
• Study Start: April 17, 2019
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: September 6, 2019

Record last verified: 2019-05

Locations

CN (1)