- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04849910
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 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
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Glen Raffel, MD, PhD
- Phone Number: 180 6176556580
- Email: clinicaltrials@vorbio.com
Study Locations
-
-
Quebec
-
Montréal, Quebec, Canada, H1T2M4
- Recruiting
- Hopital Maisonneuve-Rosemont
-
Contact:
- Lea Bernard, MD
- Phone Number: 514-252-3404
- Email: lea.bernard.med@ssss.gouv.qc.ca
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Principal Investigator:
- Lea Bernard, MD
-
-
-
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California
-
La Jolla, California, United States, 92037
- Recruiting
- University Of California San Diego Moores Cancer Center
-
Contact:
- Olivia Nolan
- Phone Number: 858-246-5794
- Email: ocnolan@health.ucsd.edu
-
Principal Investigator:
- Divya Koura, MD
-
-
Florida
-
Miami, Florida, United States, 33176
- Recruiting
- Miami Cancer Institute
-
Principal Investigator:
- Guenther Koehne, MD, PhD
-
Contact:
- Guenther Koehne, MD, PhD
- Phone Number: 786-527-8427
- Email: guentherk@baptisthealth.net
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Maryland
-
Bethesda, Maryland, United States, 20892
- Recruiting
- National Institutes of Health, Clinical Center
-
Contact:
- Monica Epstein
- Phone Number: 240-281-4207
- Email: NCILLTCT@mail.nih.gov
-
Principal Investigator:
- Nirali Shah, MD, MHSc
-
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Missouri
-
Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine Siteman Cancer Center
-
Contact:
- Brandon Christen
- Phone Number: 314-454-5096
- Email: brandon.c@wustl.edu
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Principal Investigator:
- John DiPersio, MD
-
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New Jersey
-
Hackensack, New Jersey, United States, 07601
- Terminated
- John Theurer Cancer Center at Hackensack University Medical Center
-
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New York
-
New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Center
-
Principal Investigator:
- Roni Tamari, MD
-
Contact:
- Roni Tamari, MD
- Phone Number: 646-608-3738
- Email: ABMTTrials@mskcc.org
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New York, New York, United States, 10032
- Recruiting
- Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center
-
Contact:
- Nurse Navigator
- Phone Number: 212-342-5162
- Email: cancerclinicaltrials@cumc.columbia.edu
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Principal Investigator:
- Markus Y Mapara, MD, PhD
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Ohio
-
Cleveland, Ohio, United States, 44106
- Recruiting
- University Hospitals Seidman Cancer Center
-
Contact:
- Cancer Information Service Line
- Phone Number: 800-641-2422
- Email: Crystal.Santo@UHhospitals.org
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Principal Investigator:
- Brenda Cooper, MD
-
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Washington
-
Seattle, Washington, United States, 98109
- Recruiting
- Fred Hutchinson Cancer Research Center
-
Principal Investigator:
- Roland Walter, MD, PhD, MS
-
Contact:
- Roland Walter, MD, PhD, MS
- Phone Number: 206-667-3599
- Email: rwalter@fredhutch.org
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
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) 3. AML sample from the patient must have evidence of CD33 expression (>0%) 4. Candidate for HLA-matched allogeneic HCT using a myeloablative conditioning regimen.
5. Must have a related or unrelated stem cell donor that is a 8/8 match for HLA-A, -B, -C, and -DRB1.
6. Must have adequate performance status and organ function as defined below:
a) Performance Status: Karnofsky score of ≥70. b) Cardiac: left ventricular ejection fraction (LVEF) ≥50% c) Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) ≥66%.
d) Renal: estimated glomerular filtration rate (GFR) >60 mL/min e) 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:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1
VOR33 infusion followed by Mylotarg Dose Level 1
|
Allogeneic, human leukocyte antigen (HLA) matched, genome edited hematopoietic stem and progenitor cell (HSPC) therapy product lacking the CD33 myeloid protein
Infusion of Mylotarg
Other Names:
|
Experimental: Cohort 2
VOR33 infusion followed by Mylotarg Dose Level 2
|
Allogeneic, human leukocyte antigen (HLA) matched, genome edited hematopoietic stem and progenitor cell (HSPC) therapy product lacking the CD33 myeloid protein
Infusion of Mylotarg
Other Names:
|
Experimental: Cohort 3
VOR33 infusion followed by Mylotarg Dose Level 3
|
Allogeneic, human leukocyte antigen (HLA) matched, genome edited hematopoietic stem and progenitor cell (HSPC) therapy product lacking the CD33 myeloid protein
Infusion of Mylotarg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of neutrophil engraftment
Time Frame: Day 28
|
Cumulative incidence of patients who achieve neutrophil engraftment (first day of 3 consecutive days of absolute neutrophil count (ANC) ≥500 cells/mm3) by Day 28.
|
Day 28
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to neutrophil engraftment
Time Frame: Up to approximately 28 days
|
Time to neutrophil engraftment after HCT from Day 0; calculated as the first day of 3 consecutive laboratory values obtained on separate days where the ANC is ≥500 cells/mm3.
|
Up to approximately 28 days
|
Incidence of acute GVHD Grade (G) G2-G4 and G3-G4
Time Frame: Up to 24 months
|
Up to 24 months
|
|
Incidence of chronic GVHD (all and moderate-severe)
Time Frame: Up to 24 months
|
Up to 24 months
|
|
Incidence of primary and secondary graft failure
Time Frame: Up to 24 months
|
Incidence of primary and secondary graft failure measured by day 28 post HCT.
Secondary graft failure is defined as initial neutrophil engraftment by Day 28 followed by subsequent decline.
|
Up to 24 months
|
Incidence of toxicities to determine the MTD and RP2D of Mylotarg™
Time Frame: Approximately day 60 until 24 months
|
Approximately day 60 until 24 months
|
|
Incidence of transplant-related mortality (TRM) post HCT
Time Frame: Day 100, 12 months, 24 months
|
Day 100, 12 months, 24 months
|
|
Percentage of CD33-negative myeloid cells
Time Frame: Day 28, 60, 100, 180, and Months 12 and 24
|
Percent donor myeloid chimerism and CD33-negative myeloid cells in peripheral blood.
|
Day 28, 60, 100, 180, and Months 12 and 24
|
Relapse-free Survival (RFS)
Time Frame: Months 12 and 24
|
Cumulative incidence of RFS
|
Months 12 and 24
|
Overall Survival (OS)
Time Frame: Months 12 and 24
|
OS defined as the time from HCT to the date of death from any cause
|
Months 12 and 24
|
Time to platelet recovery
Time Frame: Up to approximately 60 days
|
Time to platelet recovery defined as first day of a sustained platelet count >20,000/ μL with no platelet transfusion in the preceding seven days.
|
Up to approximately 60 days
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Preleukemia
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Immunoconjugates
- Immunotoxins
- Gemtuzumab
Other Study ID Numbers
- VBP101
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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