Trial results for a pilot study investigating peripheral stem cell transplantation (PBSCT) with ex vivo t-cell receptor alpha beta+(TCRαβ+) T cell and cluster of differentiation 19+ beta (CD19+ B) cell depletion for hemoglobinopathies were posted on ClinicalTrials.gov on 2026-04-28. The study, which included patients with Sickle Cell Disease and Thalassemia Major, reported graft failure in 2 participants with Sickle Cell Disease out of a total enrollment of 8.
Background
Sickle Cell Disease is a genetic blood disorder characterized by abnormally shaped red blood cells, leading to chronic pain, organ damage, and reduced life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure for many patients, but it carries significant risks, including graft-versus-host disease (GVHD) and graft failure. Strategies to reduce these complications, such as T-cell depletion in the graft, are actively being investigated to expand the applicability and safety of transplantation for patients with hemoglobinopathies. This pilot study explored the feasibility and outcomes of a specific peripheral stem cell transplantation approach.
Trial design
This completed pilot study, designated as Phase NA, enrolled a total of 8 participants. The trial investigated peripheral stem cell transplantation (PSCT) with ex vivo t-cell receptor alpha beta+(TCRαβ+) T cell and cluster of differentiation 19+ beta (CD19+ B) cell depletion of unrelated donor (URD) grafts using the CliniMACS device. The study included patients diagnosed with Sickle Cell Disease and Thalassemia Major.
Key results
The trial reported the following key measurements for participants with Sickle Cell Disease and Beta Thalassemia Major:
- Rate of Graft Failure:
- For Sickle Cell Disease, 2 participants experienced graft failure.
- For Beta Thalassemias Major, 0 participants experienced graft failure.
- Time to Neutrophil Engraftment:
- For Sickle Cell Disease, the mean time was 15 Days (Full Range).
- For Beta Thalassemias Major, the mean time was 13 Days (Full Range).
- Incidence of Acute Graft vs. Host Disease (GVHD):
- For Sickle Cell Disease, 2 participants experienced acute GVHD.
- For Beta Thalassemias Major, 0 participants experienced acute GVHD.
- Incidence of Chronic Graft vs. Host Disease (GVHD):
- For Sickle Cell Disease, 1 participant experienced chronic GVHD.
- For Beta Thalassemias Major, 0 participants experienced chronic GVHD.
- Number of Deaths Due to Treatment:
- For Sickle Cell Disease, 1 participant died due to treatment.
- For Beta Thalassemias Major, 0 participants died due to treatment.
- Probability of Event-free Survival (EFS):
- For Sickle Cell Disease, 5 participants had event-free survival.
- For Beta Thalassemias Major, 1 participant had event-free survival.
What this means
This pilot study provides initial data on the outcomes of peripheral stem cell transplantation with TCRαβ+ and CD19+ B cell depletion for patients with Sickle Cell Disease and Beta Thalassemia Major. The observed graft failure in 2 Sickle Cell Disease participants, along with instances of acute and chronic GVHD and one treatment-related death in this group, highlight the complex challenges associated with allogeneic transplantation. While the small enrollment of 8 participants limits the generalizability of these findings, the results contribute to the understanding of this specific transplantation approach and inform future research directions aimed at improving safety and efficacy for patients with hemoglobinopathies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04523376, titled "Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies", were posted on 2026-04-28 on clinicaltrials.gov.