NCT06765876

Brief Summary

Adult patients with refractory or relapsed CD123+ hematologic malignancies, including acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, or blastic plasmocytoid dentritic cell neoplasm will be recruited in the trial. CART123 cells will be manufatured from blood of each patient. During the production of CAR123 cells, patients may receive appropriate bridging therapy. After cells are produced, participants will undergo a single course of lymphodepleting chemotherapy and receive a single dose of CAR123 T cells. The trial will establish the recommended dose for further studies, either the Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD). Patients must be eligible for hematopoietic stem cell transplantation in order to participate in the trial.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for early_phase_1

Timeline
32mo left

Started Oct 2024

Longer than P75 for early_phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress37%
Oct 2024Dec 2028

Study Start

First participant enrolled

October 23, 2024

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

December 18, 2024

Completed
22 days until next milestone

First Posted

Study publicly available on registry

January 9, 2025

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

January 12, 2026

Status Verified

January 1, 2025

Enrollment Period

4.2 years

First QC Date

December 18, 2024

Last Update Submit

January 8, 2026

Conditions

Leukemia, Myeloid, Acute(AML)Precursor Cell Lymphoblastic Leukemia-LymphomaMyelodysplastic Syndromes (MDS)Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Keywords

CAR123 T lymphocytesCART123CD123+ Hematologic MalignanciesAnti-CD123Chimeric Antigen Receptor (CAR) T CellsAutologous T CellsHematopoietic MalignanciesImmunotherapyPersonalized MedicineBiological TherapyPhase I Clinical TrialAcute Lymphoblastic Leukemia, in RelapseAcute Lymphoblastic Leukemia, RefractoryRelapsed Myelodysplastic syndromeRelapsed Blastic Plasmacytoid Dendritic Cell NeoplasmAcute Myeloid Leukaemia Recurrent

Outcome Measures

Primary Outcomes (3)

  • Safety and tolerability of autologous CART123 cells

    Cumulative incidence of IMP-related adverse events (AEs) graded by ASTCT consensus grading criteria for Cytokine Release Syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) and by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 for other AEs

    28 Days, Months 24

  • Rate of hematological recovery

    Rate of hematological recovery, defined as absolute neutrophil count (ANC) \> 1x 10\^9/L and platelet count \> 20x10\^9/L without transfusion support. Hematological recovery before and after HSCT will be evaluated separately.

    14 Days, 28 Days, 1Year, Months 12, Months 24

  • A dose of CART123 cells for further study

    Incidence of dose-limiting toxicities (DLTs) and other safety data after IMP administration.

    14 Days, 28 Days, 1year, Months 12, Months 24

Secondary Outcomes (4)

  • Morphologic Leukemia Free State (MLFS).

    at day 14 and 28 after IMP administration.

  • Complete Remission (CR) rate

    at 28 days and at any later point after IMP administration, before and after HSCT.

  • Median Overall Survival and Overall Survival

    at one year after IMP administration.

  • Feasibility and need for allogeneic hematopoietic cell transplantation after IMP administration

    within 28 days of IMP administration

Other Outcomes (1)

  • Determination of persistence and phenotype of CART123 cells in peripheral blood and bone marrow.

    Days 1, 3, 5, 7, 14, 28, 49, 70, 100. Months 6, 12, 24.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Experimental: Autologous CAR123 T lymphocytes

Biological: Autologous CAR123 T lymphocytes

Interventions

Autologous CAR123 T lymphocytesBIOLOGICAL

Anti-CD123 Chimeric Antigen Receptor (CAR) T-Cells (CART123)

Also known as: CART123, CAR123 T Cells, Autologous T-cell Therapy
Treatment Arm

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with AML, MDS-IB2, BPDCN or ALL positive for CD123 antigen, who meet one of disease specific criteria below:
  • a) Patients with AML will be eligible if they meet one of the following criteria:
  • i) Patient with refractory AML defined as failure to achieve CR or CRi after at least 2 cycles of induction chemotherapy or 1 cycle of high dose salvage regimen or 4 cycles of venetoclax with azacytidine OR
  • ii) Second or subsequent relapse of AML OR
  • iii) Relapse after allogeneic HSCT.
  • b) Patients with ALL will be eligible if they meet one of following criteria:
  • i) disease refractory to or relapsed after CAR-19 cell therapy OR
  • ii) CD19 negative relapse ineligible for treatment with TKI inhibitors and inotuzumab ozogamicin.
  • c) Patients with BPDCN will be eligible if they meet following criteria:
  • i) Refractory or relapsing after chemotherapy with or without allogeneic stem cell transplantation.
  • d) Patients with MDS-IB2 will be eligible if they meet one of following criteria:
  • i) Disease refractory to at least four cycles of azacytidine or progression on azacytidine-based therapy OR
  • ii) Disease refractory to induction chemotherapy OR
  • iii) Relapse after haematopoietic stem cell transplantation.
  • CD123 expression on malignant cells confirmed by flow cytometry or by immunohistochemistry.
  • +5 more criteria

You may not qualify if:

  • Known hypersensitivity to any component of the IMP.
  • Allogeneic HSCT within 3 months prior to IMP administration.
  • Severe, uncontrolled active infection.
  • Life expectancy \< 8 weeks.
  • Respiratory insufficiency (need for oxygen therapy).
  • Significant liver impairment: bilirubin \> 50 µmol/L, AST or ALT \> 4 times normal upper limit.
  • Acute kidney injury with serum creatinine \> 180 µmol/L, oliguria or need for acute dialysis.
  • Heart failure with LVEF \< 50% by echocardiography.
  • Presence of active grade 3 - 4 acute GvHD or severe chronic GvHD.
  • Serious uncontrolled neurological comorbidity.
  • Vaccination with live virus vaccines in the 4 weeks before IMP administration and within 90 days after the IMP dose.
  • Women: pregnancy or breast-feeding.
  • Subjects of fertile age, unless permanent sexual abstinence is their lifestyle choice:
  • female patients of childbearing potential not willing to use a highly effective method of contraception during the study,
  • male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a highly effective method of contraception during the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ustav hematologie a krevni transfuze / Institute of Hematology and Blood Transfusion

Prague, 12800, Czechia

RECRUITING

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaMyelodysplastic SyndromesBlastic Plasmacytoid Dendritic Cell NeoplasmHematologic Neoplasms

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesBone Marrow DiseasesHistiocytic Disorders, MalignantLymphomaNeoplasms by SiteSkin NeoplasmsSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Jan Vydra, MD, PhD

    Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    PRINCIPAL INVESTIGATOR

  • Petr Lesný, MD, PhD

    Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    STUDY DIRECTOR

Central Study Contacts

Petr Lesny, MD, PhD

CONTACT

+420 221 977 629Petr.Lesny@uhkt.cz

Jan Vydra, MD, PhD

CONTACT

+420 221 977 290jan.vydra@uhkt.cz

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: Experimental: Autologous CAR123 T lymphocytes
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 18, 2024

First Posted

January 9, 2025

Study Start

October 23, 2024

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2028

Last Updated

January 12, 2026

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations

CZ(1)