Trial Title:
Donor-Derived Anti-CD33 CAR T Cell Therapy (VCAR33) in Patients With Relapsed or Refractory AML After Allogeneic Hematopoietic Cell Transplant
NCT ID:
NCT05984199
Condition:
Leukemia, Myeloid, Acute
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Conditions: Keywords:
Leukemia
Acute Myeloid Leukemia
AML
Hematopoietic stem cell transplant
HCT
CD33
Allogeneic
CAR T
CAR-T
Chimeric Antigen Receptor T Cell
CAR T Cells
CAR-T Cells
Immunotherapy
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
VCAR33
Description:
Allogeneic Anti-CD33 Chimeric Antigen Receptor (CAR) T Cell therapy
Arm group label:
MRD Positive: Cohort 1
Arm group label:
MRD Positive: Cohort 2
Arm group label:
MRD Positive: Cohort 3
Arm group label:
Morphologic Disease: Cohort 1
Arm group label:
Morphologic Disease: Cohort 2
Arm group label:
Morphologic Disease: Cohort 3
Summary:
This is a Phase 1/2, multicenter, open-label, first-in-human (FIH) study of donor-derived
anti-CD33 Chimeric Antigen Receptor (CAR) T cell therapy (VCAR33) in patients with
relapsed or refractory Acute Myeloid Leukemia (AML) after human leukocyte antigen
(HLA)-matched allogeneic hematopoietic cell transplant (alloHCT).
Detailed description:
CD33 is a preferential target for AML CAR T cell therapy due to its surface expression on
the majority (>80%) of AML blasts and due to the extensive prior clinical experience
demonstrating safety and efficacy of targeting CD33 with Mylotarg (gemtuzumab
ozogamicin). VCAR33 is being developed as a potential new treatment for patients with
relapsed/refractory (R/R) AML after alloHCT. In this Phase 1/2 trial, the safety and
efficacy of lentiviral-transduced CD33-directed CAR T cells (VCAR33) generated from the
patient's prior allogeneic stem cell donor will be tested. It is hypothesized that CAR T
cell production from healthy donors will not only eliminate delays in production due to
lymphopenia but also reduce concerns for suboptimal T cell function from exposure to
systemic immunosuppression or chemotherapeutic agents. Approximately 24 eligible patients
with R/R AML after alloHCT will be enrolled in one of two separate arms based on disease
burden (morphologic disease versus measurable residual disease (MRD ) positive). The
maximum tolerated dose of VCAR33 will be determined using a 3+3 trial design within each
arm. Dose escalation can only occur after a minimum of 3 patients have completed the
dose-limiting toxicity (DLT) observation period.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients aged ≥18 years
2. Patients must have CD33+ AML in relapse or refractory after alloHCT
3. Patients must be a recipient of an 8/8 (A, B, C, DRB1) HLA-matched related or
unrelated donor alloHCT. Patients previously transplanted with VOR33 in the VBP101
study who have R/R AML may also be considered.
4. Disease status at the time of enrollment:
1. Arm A/Morphologic disease: Defined as ≥ 5% blasts (bone marrow) post-HCT
2. Arm B/MRD positive: < 5% blasts (bone marrow) with minimal residual disease of
at least 0.1% CD33+ leukemia cells by flow cytometry
5. Performance status: ECOG 0 or 1
6. Patient must have adequate organ function as defined by:
1. Cardiac: Left ventricular ejection fraction (LVEF) ≥ 45% or fractional
shortening ≥ 28%
2. Pulmonary: Baseline oxygen saturation > 92% on room air at rest
3. Hepatic: Total bilirubin < 3x institutional upper limit of normal (ULN) (except
in case of patients with documented Gilbert's disease < 5x ULN) and aspartate
aminotransferase (AST/SGOT)/alanine aminotransferase (ALT/SGPT) < 5x
institutional ULN
4. Renal: Serum creatinine must be ≤ 1.2x institutional ULN or creatinine
clearance ≥ 60 mL/min for patients with creatinine levels above institutional
normal
7. Original alloHCT donor is available and willing to undergo apheresis
Exclusion Criteria:
1. Patients who have undergone more than one alloHCT
2. Patients who have undergone alloHCT with a mismatched unrelated donor,
haploidentical donor, or with umbilical cord blood as the stem cell source
3. Patients who will be less than 100 days post-alloHCT at the time of VCAR33 infusion.
4. Patients with any history of Grade III or IV acute GVHD or severe chronic GVHD
unless approved by the Sponsor Medical Monitor
5. Patients with evidence of ongoing active acute or chronic GVHD and are taking
systemic immunosuppressive agents (> 10 mg daily of prednisone equivalent or other
GVHD-directed treatment, including extracorporeal photopheresis). Patients with
Grade 1 acute GVHD limited to the skin or mild chronic GVHD limited to the eyes,
mouth, or skin controlled with only topical therapy are eligible.
6. Patients with active CNS disease. A lumbar puncture is not required to exclude CNS
disease in the absence of clinical signs or symptoms suggesting CNS disease.
7. Patients with the following prior therapy:
1. DLI within 28 days prior to enrollment
2. Prior treatment with any CAR T cell therapy product
8. Patients with active or uncontrolled viral, bacterial, or fungal infection
9. Patients with a history of a human immunodeficiency virus (HIV) infection or acute
or chronic active hepatitis B or C infection
10. Patients with a history of malignancy other than nonmelanoma skin cancer or
carcinoma in situ (e.g., cervix, bladder, or breast) unless disease free for at
least 3 years after the last definitive therapy
11. Female patients of childbearing potential who are pregnant or breastfeeding
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California San Diego Moores Cancer Center
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Status:
Recruiting
Contact:
Last name:
Krisma Montalvo
Phone:
858-822-5364
Email:
k1montalvo@health.ucsd.edu
Investigator:
Last name:
Divya Koura, MD
Email:
Principal Investigator
Facility:
Name:
Stanford Cancer Institute
Address:
City:
Stanford
Zip:
94305
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alyssa Kanegai
Phone:
805-657-7209
Email:
akanegai@stanford.edu
Investigator:
Last name:
Lori Muffly, MD
Email:
Principal Investigator
Facility:
Name:
Miami Cancer Institute
Address:
City:
Miami
Zip:
33176
Country:
United States
Status:
Recruiting
Contact:
Last name:
Guenther Koehne, MD, PhD
Phone:
786-527-8087
Email:
guentherk@baptisthealth.net
Investigator:
Last name:
Guenther Koehne, MD, PhD
Email:
Principal Investigator
Facility:
Name:
The University of Kansas Cancer Center
Address:
City:
Fairway
Zip:
66205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Muhammad U Mushtaq, MD
Phone:
913-945-6594
Email:
mmushtaq@kumc.edu
Investigator:
Last name:
Muhammad U Mushtaq, MD
Email:
Principal Investigator
Facility:
Name:
National Institutes of Health, Clinical Center
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nirali Shah, MD, MHSc
Phone:
240-760-6199
Email:
Nirali.Shah@nih.gov
Investigator:
Last name:
Nirali Shah, MD, MHSc
Email:
Principal Investigator
Facility:
Name:
University of Michigan Health
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Recruiting
Contact:
Last name:
John Magenau, MD
Phone:
734-936-8785
Email:
johnmage@med.umich.edu
Investigator:
Last name:
John Magenau, MD
Email:
Principal Investigator
Facility:
Name:
Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marie Ventimiglia
Phone:
313-576-9271
Email:
ventimim@karmanos.org
Investigator:
Last name:
Abhinav Deol, MD
Email:
Principal Investigator
Facility:
Name:
Masonic Cancer Center, University of Minnesota
Address:
City:
Minneapolis
Zip:
55455
Country:
United States
Status:
Recruiting
Contact:
Last name:
Joseph Maakaron, MD
Phone:
612-273-2800
Email:
bonemarrowtransplant@umn.edu
Investigator:
Last name:
Joseph Maakaron, MD
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine Siteman Cancer Center
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Whitney Anderson
Phone:
314-273-4903
Email:
whitney.anderson@wustl.edu
Investigator:
Last name:
John DiPersio, MD, PhD
Email:
Principal Investigator
Facility:
Name:
John Theurer Cancer Center at Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew McConnell
Phone:
551-996-5949
Email:
andrew.mcconnell@hmhn.org
Investigator:
Last name:
Hyung Suh, MD
Email:
Principal Investigator
Facility:
Name:
Icahn School of Medicine at Mount Sinai
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jacques Azzi, MD
Phone:
212-241-6021
Email:
jacques.azzi@mssm.edu
Contact backup:
Last name:
Jonathan Lagdameo
Phone:
212-241-8552
Email:
jonathan.lagdameo@mssm.edu
Investigator:
Last name:
Jacques Azzi, MD
Email:
Principal Investigator
Facility:
Name:
University Hospitals Seidman Cancer Center
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Status:
Recruiting
Contact:
Last name:
Cancer Information Service Line
Phone:
800-641-2422
Email:
Crystal.Santo@UHhospitals.org
Investigator:
Last name:
Brenda Cooper, MD
Email:
Principal Investigator
Facility:
Name:
University of Utah Huntsman Cancer Institute
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Collind Boyington
Phone:
801-587-4779
Email:
Collind.Boyington@hci.utah.edu
Investigator:
Last name:
Brian McClune, MD
Email:
Principal Investigator
Start date:
December 11, 2023
Completion date:
November 2026
Lead sponsor:
Agency:
Vor Biopharma
Agency class:
Industry
Source:
Vor Biopharma
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05984199
