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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
310
Banner Health - MD Anderson Cancer Center
Gilbert, Arizona, United States
NOT_YET_RECRUITINGHonor Health Cancer Transplant Institute
Scottsdale, Arizona, United States
NOT_YET_RECRUITINGCity of Hope
Duarte, California, United States
RECRUITINGStanford - School of Medicine
Stanford, California, United States
Relapse-free survival (RFS)
To determine the efficacy of TSC-101 by assessing relapse-free survival (RFS)
Time frame: 3 years
Event-free survival (EFS)
To determine the efficacy of TSC-101 by event-free survival (EFS)
Time frame: 3 years
Overall survival (OS)
To determine the efficacy of TSC-101 by overall survival (OS)
Time frame: 3 years
Time to relapse (TTR)
To determine the efficacy of TSC-101 by assessing time to relapse (TTR)
Time frame: 3 years
Changes over time in Quality of Life Score - EQ-5D-5L
To determine the efficacy of TSC-101 by tracking changes over time in quality of life scores of EQ-5D-5L
Time frame: 3 years
Changes over time in Quality of Life Score - FACT-Leu
To determine the efficacy of TSC-101 by tracking changes over time in quality of life scores of FACT-Leu
Time frame: 3 years
Changes over Quality of Life Scores in FACT-BMT
To determine the efficacy of TSC-101 by tracking changes over time in quality of life scores of FACT-BMT
Time frame: 3 years
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University of Colorado - Anschutz Cancer Center
Aurora, Colorado, United States
RECRUITINGSCRI - Colorado Blood Cancer Institute
Denver, Colorado, United States
RECRUITINGYale
New Haven, Connecticut, United States
RECRUITINGMemorial Cancer Institute
Hollywood, Florida, United States
RECRUITINGMoffitt Cancer Institute
Tampa, Florida, United States
RECRUITINGNorthside Hospital
Atlanta, Georgia, United States
RECRUITING...and 16 more locations