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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
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).High risk acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) frequently relapses despite hematopoietic stem cell transplant (HCT). Post-HCT targeted therapy to reduce relapse is limited by toxicity to the engrafted cells. VOR33, an allogeneic CRISPR/Cas9 genome-edited hematopoietic stem and progenitor cell (HSPC) therapy product, lacking the CD33 protein, is being investigated for participants with CD33+ AML or MDS at high risk for relapse after HCT to allow post-HCT targeting of residual CD33+ acute AML cells using Mylotarg™ without toxicity to engrafted VOR33 cells. Participants will undergo a myeloablative HCT with matched related or unrelated donor CD34+-selected hematopoietic stem and progenitor cells (HSPCs) engineered to remove CD33 expression (VOR33
Trial Eligibility
Inclusion Criteria: 1. Must be ≥18 and ≤70 years of age. 2. 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. 3. 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) 4. AML sample from the patient must have evidence of CD33 expression (\>0%) 5. Candidate for HLA-matched allogeneic HCT using a myeloablative conditioning regimen. 6. Must have a related or unrelated stem cell donor that is a 8/8 match for HLA-A, -B, -C, and -DRB1. 7. Must have adequate performance status and organ function as defined below: 1. Performance Status: Karnofsky score of ≥70. 2. Cardiac: left ventricular ejection fraction (LVEF) ≥50% 3. Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) ≥66%. 4. Renal: estimated glomerular filtration rate (GFR) \>60 mL/min 5. Hepatic: total bilirubin \<1.5 × ULN, or if ≥1.5 × ULN direct bilirubin \<ULN and ALT/AST \<1.5 × ULN (per institutional criteria). Exclusion Criteria: 1. Prior autologous or allogeneic stem cell transplantation. 2. 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. 3. Prior treatment with Mylotarg™ (gemtuzumab ozogamicin) in the past 3.5 months. 4. Active central nervous system (CNS) leukemia. 5. Patients diagnosed with Gilbert's syndrome. 6. Uncontrolled bacterial, viral, or fungal infections; or known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.
Study Info
Organization
Vor Biopharma
Primary Outcome
Incidence of neutrophil engraftment
Interventions
Locations Recruiting
University of California San Diego Moores Cancer Center
United States, California, La Jolla
Stanford Cancer Institute
United States, California, Stanford
Miami Cancer Institute
United States, Florida, Miami
The University of Kansas Cancer Center
United States, Kansas, Fairway
National Institutes of Health, Clinical Center
United States, Maryland, Bethesda
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