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 started
completion around
Principal Investigator
by Divya Koura, MD
Headshot of Divya Koura
Divya Koura

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

  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).

You CAN'T join if...

  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.

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

  • Divya Koura, MD
    Associate Clinical Professor, Medicine, Vc-health Sciences-schools. Authored (or co-authored) 20 research publications

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
Contact us about this trial