BSB-1001 in Patients Undergoing HLA-Matched Allogenic Hematopoietic Stem Cell Transplant for AML, ALL or MDS

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат SOC + BSB-1001 Dose Escalation Cohort
  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).
• Препарат SOC+BSB-1001 Expansion Dose
  Patients will receive BSB-1001 a single intravenous (IV) infusion on day 0 following the infusion of the CD34-allo hematopoietic cell transplant (HCT).

Первичные конечные точки

• Number of participants with treatment-emergent adverse events (TEAEs), including SAEs, GVHD and dose-limiting toxicities [Срок оценки: 365 days]
• Cellular kinetics of BSB-1001 in peripheral blood [Срок оценки: 365 days]

Вторичные конечные точки (10)

• Number of patients with relapse [Срок оценки: Through 365 days post HSCT]
• Incidence of Grades II-IV acute GVHD [Срок оценки: Through 100 days post HSCT]
• Incidence of Grades III-IV acute GVHD [Срок оценки: Through 100 days post HSCT]
• Time to neutrophil engraftment [Срок оценки: Through 365 days post HSCT]
• Time to platelet engraftment [Срок оценки: Through 365 days post HSCT]
• Incidence of moderate to severe chronic GVHD [Срок оценки: Through 365 days post HSCT]
• Overall survival [Срок оценки: Through 365 days]
• GVHD-free, relapse-free survival (GFRS) [Срок оценки: Through 365 days post HSCT]
• GVHD-free survival (GFS) [Срок оценки: Through 365 days post HSCT]
• Incidence of systemic infections [Срок оценки: Through 365 days post HSCT]

Критерии участия

Критерии включения

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

• AML diagnosed which has been treated with at least two lines of therapy\* 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 For patients in remission meeting criteria a, consolidation regimens would be considered another line of therapy of eligibility purposes
• ALL which has been with abnormal lymphoblasts ≥5% and up to 25% in bone marrow OR persistent disease-defining cytogenetic abnormality or MRD positive
• MDS after at least one line of therapy, which includes hypomethylating agent(s) and must be high or very high risk by Revised International Prognostic Scoring System (IPSS-R), monosomy, or complex karyotype or TP53 mutation.
• 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
• HLA-A\*02:01 AND HA-1 positive (either H/H or H/R).
• Suitable for one of the approved conditioning regimens as defined in the protocol.
• Patient must have an identified donor that is HA 1-negative with 10/10 matched related or unrelated donor

Критерии исключения

• Weight > 100 kg.
• Prior history of allogeneic stem cell transplantation
• Prior history of autologous stem cell transplantation within 1 year prior to the planned dosing of BSB-1001 (day 0)
• 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.
• Treatment with other investigational agents within 5 half-lives of the planned dosing of BSB-1001 (day 0).
• History of treatment with checkpoint inhibitor therapy within 3 months of transplantation.
• Other malignancy with life expectancy < 1year.
• Pregnant or lactating women.
• Uncontrolled bacterial, viral, or fungal infections at time of enrollment.
• Past or current viral infections as defined in the protocol.
• CNS involvement refractory to intrathecal chemotherapy and/or standard cranial- spinal radiation. 12 Karnofsky Performance Score < 60%.

13\. Inadequate organ function as defined in protocol.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 6 центров

• City of Hope National Medical Center — Duarte
• Moffitt Cancer Center — Tampa
• University of Michigan — Ann Arbor
• University of Minnesota — Minneapolis
• Washington University at St Louis — St Louis
• The Ohio State University — Columbus

Идентификаторы

NCT: NCT06704152 · BSB1001-CL-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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