Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML or MDS
Cancer-Related Syndrome
Leukemia
Myelodysplastic Syndromes (MDS)
18 - 70 Years, Male and Female
VBP101 (primary)
NCI-2022-00073
Summary
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).
Objectives
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 product). Mylotarg™ will be given after engraftment for up to 4 cycles. The
primary endpoint assessing safety of VOR33 will be the incidence of successful
engraftment at 28 days. Part 1 of this study will evaluate the safety of escalating
Mylotarg™ dose levels to determine the maximum tolerated dose (MTD) and recommended phase
2 dose (RP2D). Part 2 will expand the number of participants to evaluate the Mylotarg™
RP2D.
Eligibility
- 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
Treatment Sites in Georgia
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