A Phase 1 interventional study of in utero hematopoietic stem cell transplantation in Alpha Thalassemia Major, Hemoglobinopathy; with Thalassemia and Hemoglobinopathies, sponsored by University of California, San Francisco. Terminated at 1 site in United States. Open to participants aged 18 Weeks to 26 Weeks. Per ClinicalTrials.gov, last updated 2025-01-27.
Sponsored by University of California, San Francisco · Phase 1, Interventional, and Treatment
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.
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.
416 studies on the registry are indexed under Thalassemia; 67 are open to participants now.
This study's enrollment of 6 is below the median of 37 across 277 interventional studies indexed under Thalassemia.
Browse Thalassemia studies →University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.
Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.
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Exclusion Criteria:
Perform in utero hematopoietic stem cell transplantation at the time of intrauterine transplantation in fetuses with alpha-thalassemia major. The cellular product is: Semi-allogeneic, Related, Maternal Bone Marrow-Derived, Miltenyi CliniMACS Plus enriched CD34+ hematopoietic stem cells administered in utero at a dose of 1 x 10\^7-10\^9 cells/kg fetal weight with equal to or less than 1% CD3+ T cells (equivalent to 10\^5-10\^7 T cells/kg fetal weight) in a final volume of 2-5ml suspended in 5% human serum albumin in Normosol buffer (Hospira, Inc.). Stem cells will be administered immediately before the red blood cells intravenously via the umbilical vein during the clinically indicated IUT. All participants will receive one dose of stem cells but may receive additional transfusions as clinically indicated.
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.
Maternal participant tolerance of bone marrow harvest
Maternal participant tolerance of bone marrow harvest defined as not requiring interventions for preterm labor, bleeding, infection or prolonged hospitalization.
Time frame: 5 year recruitment phase to include time of bone marrow harvest through 30 days after delivery
Safety of in utero hematopoietic stem cell transplantation when performed at the same time as in utero blood transfusion for the fetal participant
safety for fetal participant defined by survival 24 hours after procedure, fetal survival till birth, neonatal survival through discharge of hospitalization and no evidence of graft versus host disease
Time frame: 5 year recruitment plus 1 year data collection phase to include time of IUHCT through 1 year after delivery
Adequate bone marrow harvest from the maternal participant
This is defined as approximately 200-300 cc of bone marrow from which 10\^7-10\^9 CD34+ cells/kg fetal weight with 10\^5-10\^7 CD3+ cells/kg fetal weight will be isolated.
Time frame: 5 year recruitment phase
successful engraftment
The primary efficacy endpoint is successful engraftment of maternal bone marrow- derived CD34+ hematopoietic stem cells measured by establishment of maternal participant donor cell chimerism equal to or greater than 1% donor cells in the circulation of the fetal recipient. Chimerism will be determined in cord blood at birth, or at a corrected gestational age of 40 weeks, if there is preterm delivery, followed weekly for the first 4 weeks of life, and monthly for one year in the infant to monitor the stability of engraftment.
Time frame: 5 year recruitment plus data collection phase to include time of IUHCT through 1 year after delivery
Plan to share: No
This study is terminated, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.
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Hydrops Fetalis
University of California, San Francisco