A Study of T-Cell Receptor Engineered Donor T Cells in Subjects Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation
Start Date
6/18/2026
Completion Date
6/1/2029
Summary
This is a multicenter, genetically-randomized, controlled, Phase 3 study evaluating the efficacy and safety of T-cell receptor-engineered donor T cells targeting HA-2 (TSC-101) administered following reduced-intensity conditioning (RIC) hematopoietic cell transplantation (HCT) in participants with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The study will compare TSC-101 plus standard of care (SOC) versus SOC alone in participants undergoing allogeneic peripheral blood stem cell transplantation from haploidentical or mismatched unrelated donors.
Detailed Description
This is a multicenter, genetically-randomized, controlled, Phase 3 study designed to evaluate the efficacy and safety of TSC-101 in adult participants with AML or MDS undergoing allogeneic peripheral blood stem cell transplantation following reduced-intensity conditioning (RIC). TSC-101 is a donor-derived, genetically engineered T-cell therapy designed to express a therapeutic T-cell receptor recognizing the HA-2 minor histocompatibility antigen presented by HLA-A\*02:01. The study is intended to evaluate whether administration of TSC-101 following transplantation can improve clinical outcomes compared with standard transplantation alone. Eligible participants are adults with AML or MDS who are candidates for first allogeneic HCT using a haploidentical or mismatched unrelated donor and post-transplant. Participants assigned to the treatment arm must be HLA-A\*02:01 positive, express HA-2, and have a study-eligible HLA-A\*02-negative donor. Participants who are HLA-A\*02:01 positive but do not have a study-eligible donor, as well as participants who are HLA-A\*02:01 negative, may be assigned to the control arm. Approximately 310 participants will be enrolled, with approximately 155 participants in each study arm. Participants assigned to the treatment arm will receive two infusions of TSC-101 following recovery after transplantation. The first infusion is planned approximately 21 days after HCT (Day +14 to Day +35), and the second infusion is planned approximately 40 days after the first infusion (40 to 68 days after Infusion 1). All participants will receive SOC transplantation procedures, including one of several protocol-specified RIC regimens followed by peripheral blood stem cell transplantation and post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GvHD) prophylaxis. Safety will be monitored through ongoing review of adverse events, laboratory assessments, and clinical evaluations. An independent Data Safety Monitoring Board (DSMB) will periodically review safety data and study conduct and make recommendations regarding continuation, modification, or termination of the study. This is an event-driven study. Participants will be followed for up to 3 years after HCT. Participants who receive at least one TSC-101 infusion will subsequently participate in a separate long-term follow-up study for up to 15 years following their final TSC-101 infusion to monitor long-term safety and survival outcomes.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
TSC-101
Control
Conditions
Locations
Banner Health - MD Anderson Cancer Center
Gilbert, Arizona 85234
United States
Honor Health Cancer Transplant Institute
Scottsdale, Arizona 85258
United States
City of Hope
Duarte, California 91010
United States
Stanford - School of Medicine
Stanford, California 94305
United States
University of Colorado - Anschutz Cancer Center
Aurora, Colorado 80045
United States
SCRI - Colorado Blood Cancer Institute
Denver, Colorado 80218
United States
Yale
New Haven, Connecticut 06510
United States
Memorial Cancer Institute
Hollywood, Florida 33021
United States
Moffitt Cancer Institute
Tampa, Florida 33612
United States
Northside Hospital
Atlanta, Georgia 30342
United States
University of Chicago
Chicago, Illinois 60607
United States
The University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
Johns Hopkins University
Baltimore, Maryland 21287
United States
Massachusetts General Hospital
Boston, Massachusetts 02114
United States
Dana-Farber Cancer Institute - Hematology/Oncology
Boston, Massachusetts 02215
United States
Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Hackensack University Medical Center
Hackensack, New Jersey 07601
United States
Mount Sinai Hospital
New York, New York 10029
United States
Columbia University - Irving Medical Center
New York, New York 10032
United States
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27599
United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania 19104
United States
Sarah Cannon Research Institute - TriStar Bone Marrow Transplant (BMT)
Nashville, Tennessee 37203
United States
St. David's South Austin Medical Center
Austin, Texas 76704
United States
Baylor University Medical Center
Dallas, Texas 75246
United States
The University of Texas - MD Anderson Cancer Center
Houston, Texas 76704
United States
Froedtert & Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States