The goal of this clinical trial is to test BSB-1001 which is a new type of cellular therapy to treat blood cancers (AML, ALL and MDS). It will evaluate the safety of BSB-1001 and also determine whether it works to prevent relapse of your cancer.
This is a first-in-human, multicenter, open-label, dose-finding study for the evaluation of an HA-1 minor histocompatibility antigen (miHA)-reactive TCR-modified T cell product (BSB-1001) derived from an HLA-matched allogenic donor, in patients with AML, ALL or MDS undergoing an HLA-matched alloHSCT who are at a high risk for relapse post-HSCT. BSB-1001 targets the HLA-A\*02:01-restricted HA-1 miHA. Enrolled patients must be HLA-A\*02:01 and HA-1-positive (H/H or H/R), with an identified HLA-matched, HA-1-negative (R/R) donor. Patients will undergo one of the following myeloablative conditioning regimens, according to standard institutional procedures, which include either fludarabine+thiotepa+total body irradiation, or busulfan+ melphalan+ fludarabine. After conditioning is completed, patients will receive the CD34-selected alloHSCT followed by BSB-1001 on day 0, without any prophylactic immunosuppression. The study is an adaptive dose escalation design with 1 to 3 cohorts to evaluate single doses of BSB-1001. Three to six patients will be enrolled in each cohort and enrolled patients will be followed until completion of the study. If the maximum tolerated dose (MTD) is reached or if a dose is deemed promising, the Sponsor may determine to either cease enrollment or open an expansion cohort at the desired dose level. The optional expansion part of the study is planned to include approximately 20 additional AML patients at the recommended dose.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Patients will receive BSB-1001 a single intravenous (IV) infusion on day 0 following the infusion of the CD34-allo hematopoietic stem cell transplant (HCT).
Patients will receive BSB-1001 a single intravenous (IV) infusion on day 0 following the infusion of the CD34-allo hematopoietic cell transplant (HCT).
City of Hope National Medical Center
Duarte, California, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITINGUniversity of Michigan
Ann Arbor, Michigan, United States
Number of participants with treatment-emergent adverse events (TEAEs), including SAEs, GVHD and dose-limiting toxicities
Incidence of TEAEs (per Common Terminology Criteria for Adverse Events \[CTCAE\])
Time frame: 365 days
Cellular kinetics of BSB-1001 in peripheral blood
Quantitation of BSB-1001 (copies per μL of genomic DNA)
Time frame: 365 days
Number of patients with relapse
Presence of malignant cells in marrow (\>5%), peripheral blood (\>1%), or extramedullary sites by histopathology after achievement of CR, CRh or CRi at any time after HSCT
Time frame: Through 365 days post HSCT
Incidence of Grades II-IV acute GVHD
Acute GVHD will be graded and assessed for response based on the MAGIC consortium scoring system
Time frame: Through 100 days post HSCT
Incidence of Grades III-IV acute GVHD
Acute GVHD will be graded and assessed for response based on the MAGIC consortium scoring system
Time frame: Through 100 days post HSCT
Time to neutrophil engraftment
Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 500/µL
Time frame: Through 365 days post HSCT
Time to platelet engraftment
Time to ≥ 50,000/µL platelets for the first of 3 consecutive days without transfusion
Time frame: Through 365 days post HSCT
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University of Minnesota
Minneapolis, Minnesota, United States
RECRUITINGWashington University at St Louis
St Louis, Missouri, United States
RECRUITINGThe Ohio State University
Columbus, Ohio, United States
RECRUITINGIncidence of moderate to severe chronic GVHD
Moderate-to-severe chronic GVHD graded according to NIH scale
Time frame: Through 365 days post HSCT
Overall survival
Defined as the time from treatment to death due to any cause
Time frame: Through 365 days
GVHD-free, relapse-free survival (GFRS)
Defined as time to any of the following events: 1) Grade III-IV aGVHD; 2) chronic GVHD requiring systemic immunosuppression; 3) primary malignancy relapse; or 4) death
Time frame: Through 365 days post HSCT
GVHD-free survival (GFS)
Defined as time to any of the following events: 1) GVHD event or 2) death from any cause
Time frame: Through 365 days post HSCT
Incidence of systemic infections
Defined as infections with a severity of Grades 3 to 5 (as graded by CTCAE v 5.0 or higher) which require treatment with systemic anti-infectives
Time frame: Through 365 days post HSCT