Tagraxofusp in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies
Trial Parameters
Brief Summary
Tagraxofusp is a protein-drug conjugate consisting of a diphtheria toxin redirected to target CD123 has been approved for treatment in pediatric and adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). This trial aims to examine the safety of this novel agent in pediatric patients with relapsed/refractory hematologic malignancies. The mechanism by which tagraxofusp kills cells is distinct from that of conventional chemotherapy. Tagraxofusp directly targets CD123 that is present on tumor cells, but is expressed at lower or levels or absent on normal hematopoietic stem cells. Tagraxofusp also utilizes a payload that is not cell cycle dependent, making it effective against both highly proliferative tumor cells and also quiescent tumor cells. The rationale for clinical development of tagraxofusp for pediatric patients with hematologic malignancies is based on the ubiquitous and high expression of CD123 on many of these diseases, as well as the highly potent preclinical activity and robust clinical responsiveness in adults observed to date. This trial includes two parts: a monotherapy phase and a combination chemotherapy phase. This design will provide further monotherapy safety data and confirm the FDA approved pediatric dose, as well as provide safety data when combined with chemotherapy. The goal of this study is to improve survival rates in children and young adults with relapsed hematological malignancies, determine the recommended phase 2 dose (RP2D) of tagraxofusp given alone and in combination with chemotherapy, as well as to describe the toxicities, pharmacokinetics, and pharmacodynamic properties of tagraxofusp in pediatric patients. About 54 children and young adults will participate in this study. Patients with Down syndrome will be included in part 1 of the study.
Eligibility Criteria
Inclusion Criteria: Age * Patients must be ≥ 1 and ≤21 years of age at the time of study enrollment. Diagnosis * Relapsed and/or refractory hematologic malignancy (including, but not limited to, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, mixed phenotype acute leukemia, acute undifferentiated leukemia, blastic plasmacytoid dendritic cell neoplasm, Hodgkin lymphoma, and non-Hodgkin lymphoma). * Tumor cells must demonstrate surface expression of CD123 at the time of enrollment by flow cytometry or immunohistochemistry, as defined by the local institution. Disease Status: Monotherapy, Part 1 * Second or greater relapse; or * Refractory after 2 or more chemotherapy cycles; or * First relapse after primary chemotherapy-refractory disease; or * BPDCN in first relapse or refractory after 1 or more chemotherapy cycles Combination therapy, Part 2 * First or greater relapse; or * Refractory after 2 or more chemotherapy cycles; or * BPDCN in first relapse or re