NCT02986698

In Utero Hematopoietic Stem Cell Transplantation for Alpha-thalassemia Major (ATM)

A Single-Center, Non-Randomized Study of the Safety and Efficacy of In Utero Hematopoietic Stem Cell Transplantation for the Treatment of Fetuses With Alpha Thalassemia Major

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 18 Weeks – 26 Weeks
• Healthy volunteers: Not accepted

Summary

The investigators aims to evaluate the safety of in utero hematopoietic stem cell transplantation in fetuses with alpha-thalassemia major performed at the time of in utero transfusion of red blood cells.

Detailed description

Alpha thalassemia major (ATM) is almost universally fatal in utero and represents an orphan disease with an unmet need for effective therapies. The only current treatment to allow the fetus to be born is to perform in utero transfusions (IUT) of red blood cells to treat the anemia and avoid the complications of hydrops and fetal demise. Often, affected pregnancies undergo elective termination after diagnosis. Cases with prenatal diagnosis of ATM who receive IUT and survive to birth will ultimately require lifelong monthly blood transfusions or bone marrow transplant, if a suitable donor is identified. This is a phase 1 clinical trial to demonstrate the safety, feasibility and efficacy of performing in utero stem cell transplantation on fetuses affected with ATM. The investigators aim to recruit ten participants with a prenatal diagnosis of ATM. Participants will undergo bone marrow harvest and an in utero transfusion combined with maternal stem cells. Transplanting maternal cells into the fetus takes advantage of existing maternal-fetal tolerance during pregnancy. Hematopoietic stem cell (HSC) transplantation into the fetus takes advantage of the developing fetal immune system to induce tolerance to the transplanted cells without using conditioning or immunosuppression. Performing stem cell transplantation at the same time as IUT minimizes any additional procedural risk to the fetus. The investigators hope to demonstrate that it is safe and feasible to perform in utero stem cell transplantation. Additionally, the investigators want to demonstrate postnatal chimerism of maternal cells so that, if a bone marrow transplant remains necessary after delivery, conditioning and immune suppression will not be required.

Conditions

• Alpha Thalassemia Major
• Hemoglobinopathy; With Thalassemia
• Hemoglobinopathies
• Fetal Anemia
• Fetal Hydrops
• Alpha; Thalassemia
• Thalassemia Major
• Thalassemia Alpha
• A-Thalassemia

Interventions

Type	Name	Description
BIOLOGICAL	in utero hematopoietic stem cell transplantation	This is a phase 1 safety study to demonstrate it is safe for both the mother and fetus to perform In utero hematopoietic stem cell transplantation of maternal derived stem cells at the time of intrauterine transplantation of red blood cells to treat fetuses affected with alpha-thalassemia major.

Timeline

• Start date: 2017-10-05
• Primary completion: 2024-04-30
• Completion: 2024-12-31
• First posted: 2016-12-08
• Last updated: 2025-01-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study