Clinical trial NCT06704152: BSB-1001 in Patients Undergoing HLA-Matched Allogenic Hematopoietic Stem Cell Transplant for AML, ALL or MDS
Official title: A Phase 1/2a Multicenter Ascending Dose Study to Evaluate the Safety of HA-1 Minor Histocompatibility Antigen-Reactive TCR-Modified T Cells (BSB-1001) in Patients Undergoing HLA-Matched Allogenic Hematopoietic Stem Cell Transplant for AML, ALL or MDS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: AML, Adult Recurrent
ALL, Recurrent, Adult
MDS
Keywords: TCR, T-cell therapy
Lead sponsor: BlueSphere Bio, Inc
Sponsor class: INDUSTRY
First posted: 2024-11-25
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients, ages 18 - 70 years inclusive, undergoing alloHCT.
2. Any Any of the following high-risk hematologic malignancies:

   1. AML diagnosed which has been treated with at least two lines of therapy, and refractory or relapsed (CR, CRh or CRi,), including myeloblasts up to 25% OR MRD positive OR persistent disease-defining cytogenetic abnormality OR MRD-negative, but with high-risk disease
   2. ALL which has been with abnormal lymphoblasts ≥5% and up to 25% in bone marrow OR persistent disease-defining cytogenetic abnormality or MRD positive
   3. MDS after at least one line of therapy, which includes hypomethylating agent(s) and venetoclax and must be high or very high risk by Revised International Prognostic Scoring System (IPSS-R), monosomy, or complex karyotype or TP53 mutation.
   4. In the expansion phase AML patients diagnosed which has been treated with at least two lines of therapy, and refractory or relapsed (CR, CRh or CRi,), including myeloblasts up to 25% OR MRD positive OR persistent disease-defining cytogenetic abnormality OR MRD-negative, but with high- risk disease
3. HLA-A\*02:01 AND HA-1 positive (either H/H or H/R).
4. Suitable for one of the approved conditioning regimens as defined in the protocol.
5. Patient must have an identified donor that is HA 1-negative with 10/10 matched related donor or 12/12 matched unrelated donor

Exclusion Criteria:

1. Weight \> 100 kg.
2. Prior history of allogeneic or autologous stem cell transplantation.
3. Previous genetically engineered chimeric antigen receptor T Cell therapy (CAR-T), approved or investigational, within 2 years of screening, with the exception of patients with ALL previously treated with an autologous CAR-T product.
4. Treatment with other investigational agents within 5 half-lives of the planned dosing of BSB-1001 (day 0).
5. History of treatment with checkpoint inhibitor therapy within 3 months of t transplantation.
6. Other malignancy with life expectancy \< 1year.
7. Pregnant or lactating women.
8. Uncontrolled bacterial, viral, or fungal infections at time of enrollment.
9. Past or current viral infections as defined in the protocol.
10. CNS involvement refractory to intrathecal chemotherapy and/or standard cranial- spinal radiation.
11. Karnofsky Performance Score \< 60%.
12. Inadequate organ function as defined in protocol.

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAEs), including SAEs, GVHD and dose-limiting toxicities
timeFrame: 365 days
measure: Cellular kinetics of BSB-1001 in peripheral blood
timeFrame: 365 days
Secondary outcomes:
measure: Number of patients with relapse
timeFrame: Through 365 days post HSCT
measure: Incidence of Grades II-IV acute GVHD
timeFrame: Through 100 days post HSCT
measure: Incidence of Grades III-IV acute GVHD
timeFrame: Through 100 days post HSCT
measure: Time to neutrophil engraftment
timeFrame: Through 365 days post HSCT
measure: Time to platelet engraftment
timeFrame: Through 365 days post HSCT
measure: Incidence of moderate to severe chronic GVHD
timeFrame: Through 365 days post HSCT
measure: Overall survival
timeFrame: Through 365 days
measure: GVHD-free, relapse-free survival (GFRS)
timeFrame: Through 365 days post HSCT
measure: GVHD-free survival (GFS)
timeFrame: Through 365 days post HSCT
measure: Incidence of systemic infections
timeFrame: Through 365 days post HSCT
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Washington University at St Louis
state: Missouri
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
References: