Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML or MDS
a study on Leukemia Myelodysplastic Syndrome Acute Myeloid Leukemia Bone Marrow Transplant Hematopoietic Cell Transplantation Stem Cell Transplant Transplants
Summary
- Eligibility
- for people ages 18-70 (full criteria)
- Location
- at La Jolla, California and other locations
- Dates
- study startedcompletion around
- Principal Investigator
- by Divya Koura, MD
Description
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).
Official Title
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
Details
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.
Keywords
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Acute Myeloid Leukemia, AML, Hematopoietic stem cell transplant, HCT, CD33, Allogeneic, Myelodysplastic Syndromes with excess blasts, MDS, MDS-EB, Cell therapy, Preleukemia, Myeloid Leukemia, Syndrome, Gemtuzumab, VOR33, Mylotarg
Eligibility
You can join if…
Open to people ages 18-70
- 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).
You CAN'T join if...
- Prior autologous or allogeneic stem cell transplantation.
- 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.
- Prior treatment with Mylotarg™ (gemtuzumab ozogamicin) in the past 3.5 months.
- Active central nervous system (CNS) 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.
Locations
- University of California San Diego Moores Cancer Center
accepting new patients
La Jolla California 92037 United States - Stanford Cancer Institute
accepting new patients
Stanford California 94305 United States
Lead Scientist at UCSD
Details
- Status
- accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Vor Biopharma
- ID
- NCT04849910
- Phase
- Phase 1/2 research study
- Study Type
- Interventional
- Participants
- Expecting 24 study participants
- Last Updated
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