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

Prior treatment

• Allogeneic HSCT within 3 months prior to IMP administration.
• Vaccination with live virus vaccines in the 4 weeks before IMP administration and within 90 days after the IMP dose.

Other illness

• Known hypersensitivity to any component of the IMP.
• Severe, uncontrolled active infection.
• Respiratory insufficiency (need for oxygen therapy).

Lab values

• 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.

Age

• 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.

Other

• Life expectancy \< 8 weeks.
• Presence of active grade 3 - 4 acute GvHD or severe chronic GvHD.
• Serious uncontrolled neurological comorbidity.
• Women: pregnancy or breast-feeding.

• Patients with AML, MDS-IB2, BPDCN or ALL positive for CD123 antigen, who meet one of disease specific criteria below:
  • Patients with AML will be eligible if they meet one of the following criteria:
  • 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
  • Second or subsequent relapse of AML OR
  • Relapse after allogeneic HSCT.
  • Patients with ALL will be eligible if they meet one of following criteria:
  • disease refractory to or relapsed after CAR-19 cell therapy OR
  • CD19 negative relapse ineligible for treatment with TKI inhibitors and inotuzumab ozogamicin.
  • Patients with BPDCN will be eligible if they meet following criteria:
  • Refractory or relapsing after chemotherapy with or without allogeneic stem cell transplantation.
  • Patients with MDS-IB2 will be eligible if they meet one of following criteria:
  • Disease refractory to at least four cycles of azacytidine or progression on azacytidine-based therapy OR
  • Disease refractory to induction chemotherapy OR
  • Relapse after haematopoietic stem cell transplantation.
• CD123 expression on malignant cells confirmed by flow cytometry or by immunohistochemistry.
• Age between 18 and 70 years.
• Patient has a suitable donor for allogeneic hematopoietic stem cell transplantation. Workup and clearance of the donor must be completed before IMP administration.
• Patient able to understand and sign informed consent.
• Women of child-bearing potential: negative pregnancy test at enrolment (PSV) and at Visit 1.
• Patient for whom there are no standard-of-care treatments available or such treatment options have been exhausted.