CART123 T Cells in Relapsed or Refractory CD123+ Hematologic Malignancies: a Dose Escalation Phase I Trial

Launched by INSTITUTE OF HEMATOLOGY AND BLOOD TRANSFUSION, CZECH REPUBLIC · Jan 3, 2025

Keywords

ClinConnect Summary

This clinical trial is testing a new treatment called CART123 T cells for adults with certain types of blood cancers that have not responded to previous treatments. These cancers include acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN), and others that are positive for a marker called CD123. To participate, patients need to be between 18 and 70 years old, have a suitable donor for a stem cell transplant, and have run out of standard treatment options. The trial aims to find out the best dose of the CART123 T cells that can be safely given to patients.

Participants can expect to have their own immune cells collected and modified in a lab to recognize and attack cancer cells. Before receiving the CART123 T cells, they will undergo chemotherapy to prepare their bodies. Throughout the process, patients may have access to other supportive treatments. It’s important for potential participants to know that this trial is for those whose cancers have either come back or have not responded to other therapies, and they need to meet specific health criteria to join.

Gender

ALL

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.