CART123 T cells for treating relapsed or refractory blood cancers

Safety and Efficacy of Anti-CD123 Chimeric Antigen Receptor-Modified Autologous T Cells (CART123) in Patients With Relapsed/Refractory CD123+ Hematologic Malignancies: A Dose Escalation, Open-Label, Phase I Study

This study is testing a new treatment using specially modified T cells to see if it can help adults with certain tough-to-treat blood cancers feel better.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Institute of Hematology and Blood Transfusion, Czech Republic (other)
• Drugs / interventions: inotuzumab, chemotherapy
• Locations: 1 site (Prague)
• Trial ID: NCT06765876 on ClinicalTrials.gov

What this trial studies

This clinical trial focuses on adult patients with relapsed or refractory CD123+ hematologic malignancies, such as acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm. Participants will receive autologous CAR123 T lymphocytes after undergoing a lymphodepleting chemotherapy regimen. The trial aims to determine the optimal dosing of CART123 cells using an accelerated Bayesian optimal interval design. Patients must be eligible for hematopoietic stem cell transplantation and have a donor identified.

Who should consider this trial

Good fit: Ideal candidates are adults with refractory or relapsed CD123+ hematologic malignancies who are eligible for hematopoietic stem cell transplantation.

Not a fit: Patients with CD123-negative hematologic malignancies or those not eligible for stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat blood cancers.

How similar studies have performed: While CAR T-cell therapies have shown success in other hematologic malignancies, this specific approach targeting CD123 is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. CD123 expression on malignant cells confirmed by flow cytometry or by immunohistochemistry.
3. Age between 18 and 70 years.
4. Patient has a suitable donor for allogeneic hematopoietic stem cell transplantation. Workup and clearance of the donor must be completed before IMP administration.
5. Patient able to understand and sign informed consent.
6. Women of child-bearing potential: negative pregnancy test at enrolment (PSV) and at Visit 1.
7. Patient for whom there are no standard-of-care treatments available or such treatment options have been exhausted.

Exclusion Criteria:

1. Known hypersensitivity to any component of the IMP.
2. Allogeneic HSCT within 3 months prior to IMP administration.
3. Severe, uncontrolled active infection.
4. Life expectancy \< 8 weeks.
5. Respiratory insufficiency (need for oxygen therapy).
6. Significant liver impairment: bilirubin \> 50 µmol/L, AST or ALT \> 4 times normal upper limit.
7. Acute kidney injury with serum creatinine \> 180 µmol/L, oliguria or need for acute dialysis.
8. Heart failure with LVEF \< 50% by echocardiography.
9. Presence of active grade 3 - 4 acute GvHD or severe chronic GvHD.
10. Serious uncontrolled neurological comorbidity.
11. Vaccination with live virus vaccines in the 4 weeks before IMP administration and within 90 days after the IMP dose.
12. Women: pregnancy or breast-feeding.
13. Subjects of fertile age, unless permanent sexual abstinence is their lifestyle choice:

    1. female patients of childbearing potential not willing to use a highly effective method of contraception during the study,
    2. 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.

Where this trial is running

Prague

• Ustav hematologie a krevni transfuze / Institute of Hematology and Blood Transfusion — Prague, Czechia (RECRUITING)

Study contacts

• Principal investigator: Jan Vydra, MD, PhD — Institute of Hematology and Blood Transfusion, Prague, Czech Republic
• Study coordinator: Petr Lesny, MD, PhD

Conditions: Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Blastic Plasmacytoid Dendritic Cell Neoplasm, CAR123 T lymphocytes, CART123, CD123+ Hematologic Malignancies, Anti-CD123