Safety and Efficacy of Anti-CD123 CAR-T Therapy in Patients With Refractory/ Relapsed CD123+ Acute Myeloid Leukemia.

NCT04014881 | Unknown Phase 1

• 1 other identifier: WHUH-CART-CD123-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia.

Conditions

CD123+ Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-related Adverse Events

  Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).

  3 years

Secondary Outcomes (6)

• Overall remission rate(ORR) of anti-CD123 CAR-T Therapy in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia

  3 years

• Overall survival(OS) of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia

  3 years

• Duration of Response(DOR) of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia

  3 years

• Progress-free survival(PFS) of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia

  3 years

• Rate of anti-CD123 CAR-T cells in bone marrow cells and peripheral blood cells

  3 years

Study Arms (1)

CD123+ Acute Myeloid Leukemia

EXPERIMENTAL

Patients will receive CD123-targeted CAR-T cells in the dose-climbing trial. Each dose group has 3 patients and the the maximum dose can be extended.

Biological: Third-generation anti-CD123 CAR-T cells

Interventions

Third-generation anti-CD123 CAR-T cells BIOLOGICAL

From the minimum dose, If no DLT emerges in the group, then the next group uses the subsequent higher dose. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level.

CD123+ Acute Myeloid Leukemia

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathological and histological examination confirmed CD123+ refractory or relapsed Acute Myeloid Leukemia.
• A. Diagnostic criteria for recurrent AML: After complete remission (CR), leukemia cells or bone marrow primordial cells \> 0.050 (except for bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration appears again in peripheral blood.
• B．Diagnostic criteria for refractory AML(Meeting one of the following)
• i. ineffectiveness after the first standard regimen treatment of 2 courses.
• ii. patients relapse within 12 months after consolidation and intensive treatment after CR.
• iii. Patients relapse 12 months later and fail to respond to conventional chemotherapy.
• iv. Patients with two or more recurrences.
• v. Patients with persistent extramedullary leukemia.
• vi. Patients with recurrence after CR and unsuitable for HSCT (auto/allo-HSCT).
• Aged 18 to 70 years (including 18 and 70 years old).
• At least one measurable or evaluable lesion：AML patients with positive or relapsed positive bone marrow MRD.
• ECOG≤ 2 and expected lifetime ≥3 months.
• Adequate organ function:
• A. Liver function: ALT/AST≤3 ULN. Total bilirubin≤2 ULN.
• B. Renal function: eGFR\> 60 mL/min/1.73 m2, or creatinine clearance ≥45mL/min.

You may not qualify if:

• Women who are pregnant (urine/blood pregnancy test positive) or lactating.
• Male or female with a conception plan in the past 1 years.
• Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment.
• Uncontrolled infectious disease within 4 weeks prior to enrollment.
• Active hepatitis B/C virus.
• HIV infected patients.
• Suffering from a serious autoimmune disease or immunodeficiency disease.
• The patient is allergic and is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
• The patient participated in other clinical trials within 6 weeks prior to enrollment.
• Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
• Suffering from mental illness.
• Patient has drug abuse/addiction.
• Central nervous system involvement.
• According to the investigator's judgment, the patient has other unsuitable grouping conditions.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Wuhan Bio-Raid Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Related Publications (6)

• Hansrivijit P, Gale RP, Barrett J, Ciurea SO. Cellular therapy for acute myeloid Leukemia - Current status and future prospects. Blood Rev. 2019 Sep;37:100578. doi: 10.1016/j.blre.2019.05.002. Epub 2019 May 11.

  PMID: 31109711 BACKGROUND

• Arcangeli S, Rotiroti MC, Bardelli M, Simonelli L, Magnani CF, Biondi A, Biagi E, Tettamanti S, Varani L. Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia. Mol Ther. 2017 Aug 2;25(8):1933-1945. doi: 10.1016/j.ymthe.2017.04.017. Epub 2017 May 4.

  PMID: 28479045 BACKGROUND

• Cartellieri M, Feldmann A, Koristka S, Arndt C, Loff S, Ehninger A, von Bonin M, Bejestani EP, Ehninger G, Bachmann MP. Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts. Blood Cancer J. 2016 Aug 12;6(8):e458. doi: 10.1038/bcj.2016.61.

  PMID: 27518241 BACKGROUND

• Tettamanti S, Biondi A, Biagi E, Bonnet D. CD123 AML targeting by chimeric antigen receptors: A novel magic bullet for AML therapeutics? Oncoimmunology. 2014 May 14;3:e28835. doi: 10.4161/onci.28835. eCollection 2014.

  PMID: 25083319 BACKGROUND

• Tasian SK, Kenderian SS, Shen F, Ruella M, Shestova O, Kozlowski M, Li Y, Schrank-Hacker A, Morrissette JJD, Carroll M, June CH, Grupp SA, Gill S. Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia. Blood. 2017 Apr 27;129(17):2395-2407. doi: 10.1182/blood-2016-08-736041. Epub 2017 Feb 28.

  PMID: 28246194 BACKGROUND

• Mardiros A, Dos Santos C, McDonald T, Brown CE, Wang X, Budde LE, Hoffman L, Aguilar B, Chang WC, Bretzlaff W, Chang B, Jonnalagadda M, Starr R, Ostberg JR, Jensen MC, Bhatia R, Forman SJ. T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood. 2013 Oct 31;122(18):3138-48. doi: 10.1182/blood-2012-12-474056. Epub 2013 Sep 12.

  PMID: 24030378 BACKGROUND

Study Officials

• Heng Mei, M.D., Ph.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yu Hu, M.D., Ph.D

CONTACT

86-13986183871; dr_huyu@126.com

Heng Mei, M.D., Ph.D

CONTACT

86-13886160811; hmei@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study was a single-center, open-label, single-arm, non-randomized,3+3 dose escalation clinical trial.Each dose group has 3 patients.If no DLT emerges in the group, then the next group uses the subsequent higher dose. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level. The maximum dose could be extended.

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 10, 2019
• Study Start: July 6, 2019
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2022
• Last Updated: August 7, 2019

Record last verified: 2019-08

Locations

CN (1)