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

a study on Leukemia Acute Myeloid Leukemia Bone Marrow Transplant Hematopoietic Cell Transplantation Transplants

Summary

Eligibility
for people ages 18-70 (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion
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 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) 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 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, Leukemia, Acute Myeloid Leukemia, AML, Hematopoietic stem cell transplant, HCT, CD33, Allogeneic, Myeloid Leukemia, Gemtuzumab, VOR33, Mylotarg

Eligibility

You can join if…

Open to people ages 18-70

  1. Must be ≥18 and ≤70 years of age.
  2. Must have confirmed diagnosis of AML in first or second complete remission (CR1 or CR2) or have bone marrow blasts ≤10% without circulating blasts.
  3. AML sample from the patient must have evidence of CD33 expression (>0%)
  4. AML must have intermediate or high-risk disease-related genetics and the presence of minimal residual disease (MRD). Subjects in CR2 or with persistent morphologic blasts; may have favorable disease-related genetics.
  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 10/10 match for HLA-A, -B, -C, -DRB1 and -DQB1.
  7. Must have adequate performance status and organ function as defined below:
  8. Performance Status: Karnofsky score of ≥70.
  9. Cardiac: left ventricular ejection fraction (LVEF) ≥50%
  10. Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) ≥66%.
  11. Renal: estimated glomerular filtration rate (GFR) >60 mL/min
  12. 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).
  4. Active central nervous system (CNS) leukemia or history of other active malignancy(ies).
  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
  • Fred Hutchinson Cancer Research Center accepting new patients
    Seattle Washington 98109 United States

Lead Scientist at UCSD

  • Divya Koura, MD
    Associate Clinical Professor, Medicine, Vc-health Sciences-schools. Authored (or co-authored) 12 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 18 study participants
Last Updated
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