Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML or MDS

Trial details

Who runs it

Vor Biopharma

Trial code

NCT04849910

Record updated

2025. július 29.

Original description

This is a Phase 1/2a, multicenter, open-label, first-in-human (FIH) study of VOR33 in participants with AML or MDS who are undergoing human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (HCT).Read full original descriptionShow less

A First-In-Human, Open-Label, Multicenter Study of VOR33 in Patients With Acute Myeloid Leukemia Who Are at High-Risk for Leukemia Relapse Following Hematopoietic Cell Transplantation

This is a Phase 1/2a, multicenter, open-label, first-in-human (FIH) study of VOR33 in participants with AML or MDS who are undergoing human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (HCT).

Inclusion: Must be ≥18 and ≤70 years of age; Patients with AML must have one of the following groups of features that are known to be a risk factor for leukemia relapse:; BM in morphological remission (<5% blasts) with adverse-risk disease related genetics at presentation (according to European Leukemia-Net guidelines [ELN, Döhner 2017]), or; Intermediate risk genetics in morphologic remission (<5% blasts) with other recognized high risk criteria such as MRD+ following therapy, or; BM with evidence of persistent leukemia 5-10% blasts post induction/salvage therapy. Patients with BM Blast count >10% may participate with Sponsor Medical Monitor approval. (Note: these patients may have disease-related genetics of any risk criteria at presentation), or; Any patient in second or greater remission; Patients with MDS must have all of the following:; Previous or current IPSS-R score of High or Very High risk; AND; Previous or current MDS-IB1 or MDS-IB2 per the 2022 WHO criteria (Khoury 2022); AML sample from the patient must have evidence of CD33 expression (>0%); Candidate for HLA-matched allogeneic HCT using a myeloablative conditioning regimen; Must have a related or unrelated stem cell donor that is a 8/8 match for HLA-A, -B, -C, and -DRB1; Must have adequate performance status and organ function as defined below:; Performance Status: Karnofsky score of ≥70; Cardiac: left ventricular ejection fraction (LVEF) ≥50%; Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) ≥66%; Renal: estimated glomerular filtration rate (GFR) >60 mL/min; Hepatic: total bilirubin <1.5 × ULN, or if ≥1.5 × ULN direct bilirubin <ULN and ALT/AST <1.5 × ULN (per institutional criteria).

Exclusion: Prior autologous or allogeneic stem cell transplantation; Prior treatment with Mylotarg™ (gemtuzumab ozogamicin) in the past 3.5 months; Presence of the following disease-related genetics: t(15; 17)(q22; q21), or t(9; 22)(q34; q11), or other evidence of acute promyelocytic leukemia or chronic myeloid leukemia; Patients diagnosed with Gilbert's syndrome; Uncontrolled bacterial, viral, or fungal infections; or known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection; Active central nervous system (CNS) leukemia.

ClinicalTrials.gov NCT04849910