Trial Title:
SENTI-202: Off-the-shelf Logic Gated CAR NK Cell Therapy in Adults With CD33 and/or FLT3 Blood Cancers Including AML/MDS
NCT ID:
NCT06325748
Condition:
AML/MDS
CD33 Expressing Hematological Malignancies
FLT3 Expressing Hematological Malignancies
Conditions: Official terms:
Neoplasms
Hematologic Neoplasms
Cytarabine
Fludarabine
Conditions: Keywords:
SENTI-202
CAR NK
natural killer cell
CD33
FLT3
allogeneic
logic gate
relapsed/refractory AML
relapsed/refractory MDS
inhibitory CAR
activating CAR
NOT logic gate
IL15
interleukin 15
cell therapy
off-the-shelf
leukemic stem cells
blastic plasmacytoid dendritic cell neoplasm (BPDCN)
multiple myeloma (MM)
mixed phenotype acute leukemia (MPAL)
endomucin
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
SENTI-202
Description:
SENTI-202 is an investigational off-the-shelf CAR NK cell therapy designed to selectively
target and eliminate CD33 and/or FLT3 expressing hematological malignancies while sparing
healthy cells using a NOT logic gate.
SENTI-202 is administered in 3 weekly doses (Days 0, 7, 14) of a 28-day treatment cycle
following a lymphodepletion conditioning regimen of fludarabine and cytarabine
(flu/Ara-C). Subjects will receive a minimum of 1 and maximum of 3 treatment cycles.
Arm group label:
SENTI-202 CAR NK cell therapy
Other name:
Fludarabine
Other name:
Cytarabine (ara-C)
Summary:
This is an open-label study of the safety, biodynamics, and anti-cancer activity of
SENTI-202 (an off-the-shelf logic gated CAR NK cell therapy) in patients with CD33 and/or
FLT3 expressing blood cancers, including AML and MDS.
Detailed description:
This is a dose-finding study of SENTI-202, comprised of an initial dose finding using a
modified "3+3" study design to determine the maximum tolerated dose (MTD) and recommended
phase two dose (RP2D) of SENTI-202 when administered after lymphodepleting chemotherapy
(Part 1) followed by disease-specific expansion cohorts at the RP2D (Part 2).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Subjects with CD33 and/or FLT3 expressing malignancies, including:
- Relapsed refractory acute myeloid leukemia (AML) with morphologic relapse as
defined by ≥5% bone marrow blasts who have received at least 1 prior line, but
no more than 3 prior lines of standard anti-AML therapy. Subjects with
FLT3-mutated or IDH ½-mutated disease must have received at least one prior
targeted therapy.
- Relapsed refractory myelodysplastic syndrome (MDS) with increased blasts who
have received at least 1 prior line, but no more than 2 prior lines of anti-MDS
therapy
- Other hematological malignancies who have received at least 1 prior line of
standard of care for the respective disease
- Documentation of CD33 expression (or FLT3 expression if available) by
individual institutional standard of care
- ECOG performance score of 0-1
- Adequate organ function including platelet count >20x109/L (platelet transfusion is
permitted)
- Adequate recovery from toxicities from previous cancer treatments, as described in
the study protocol
- Willing and able to provide written informed consent
Exclusion Criteria:
- White blood cell (WBC) count of ≥20×109/L or circulating blasts ≥10×109/L or rapidly
progressive/hyperproliferative disease
- Acute promyelocytic leukemia with t(15;17) (q22;q12) or abnormal promyelocytic
leukemia/retinoic acid receptor alpha (APML-RARA)
- MDS with fibrosis (MDS-f) or known prior history of constitutional
conditions/syndromes with chemo-responsive AML
- Evidence of leukemic meningitis or known active central nervous system disease
- Presence of extra-medullary disease or myeloid sarcoma alone with no morphologic
hematologic relapse
- Prior use of certain anti-cancer therapies and/or use within a certain number of
days prior to SENTI-202 study treatment, as described in the study protocol
- Hematopoietic cell transplantation (HCT) less than 100 days prior to the first dose
of SENTI-202
- Prior NK cell or CAR T cell therapy at any time
- Prior donor lymphocyte infusion (DLI), except if after HCT for MRD+ disease
- Medical conditions or medications prohibited by the study protocol
- Pregnant or breastfeeding female
Gender:
All
Minimum age:
18 Years
Maximum age:
74 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
UCLA Medical Center
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bruck Habtemariam
Contact backup:
Phone:
310-794-0242
Investigator:
Last name:
Gary Schiller, MD
Email:
Principal Investigator
Facility:
Name:
Colorado Blood Cancer Institute
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sarah Cannon Research Institute
Phone:
844-482-4812
Investigator:
Last name:
Alireza Eghtedar, MD
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic
Address:
City:
Jacksonville
Zip:
32224
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Hemant Murthy, MD
Investigator:
Last name:
Hemant Murthy, MD
Email:
Principal Investigator
Facility:
Name:
TriStar Bone Marrow Transplant
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sarah Cannon Research Institute
Phone:
844-482-4812
Investigator:
Last name:
Stephen Strickland, MD
Email:
Principal Investigator
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Farhad Ravandi, MD
Investigator:
Last name:
Farhad Ravandi, MD
Email:
Principal Investigator
Facility:
Name:
Methodist Healthcare
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sarah Cannon Research Institute
Phone:
844-482-4812
Investigator:
Last name:
Nosha Farhadfar, MD
Email:
Principal Investigator
Facility:
Name:
Royal Prince Alfred Hospital
Address:
City:
Camperdown
Zip:
2050
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Edward Abadir
Investigator:
Last name:
Edward Abadir, MBBS FRACP FRCPA
Email:
Principal Investigator
Facility:
Name:
Peter MacCallum Cancer Center
Address:
City:
Melbourne
Zip:
3000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Ashish Bajel
Investigator:
Last name:
Ashish Bajel, MBBS FRACP FRCPA
Email:
Principal Investigator
Start date:
April 22, 2024
Completion date:
August 2040
Lead sponsor:
Agency:
Senti Biosciences
Agency class:
Industry
Source:
Senti Biosciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06325748
