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Prenatal Transplantation for Fetuses With Fanconi Anemia

a study on Anemia Fanconi Anemia Bone Disease DNA Repair-Deficiency Disorders Cancer Predisposition Syndrome Bone Marrow Transplant Hematopoietic Cell Transplantation Stem Cell Transplant

Summary

Location
at San Francisco, California and other locations
Dates
study started
study ends around
Principal Investigator
by Tippi MacKenzie, MD
Headshot of Tippi MacKenzie
Tippi MacKenzie

Description

Summary

The investigators aim to evaluate the safety and effectiveness of In Utero Hematopoietic Stem Cell Transplant (IUHSCT) for the treatment of fetuses diagnosed with Fanconi anemia (FA) while in the womb.

Official Title

A Phase I/II, Non-Randomized Study of the Safety and Efficacy of In Utero Hematopoietic Stem Cell Transplantation for the Treatment of Fanconi Anemia in Affected Fetuses

Details

Fanconi Anemia (FA) is a genetic disorder known for shortening the lifespans of those diagnosed due to chromosomal fragility that leads to hematopoietic failure (aplastic anemia, myelodysplasia, or leukemia), increased cancer risk, and other possible rare organ dysfunction such as congenital structural anomalies. Importantly, 80-90% of FA patients develop bone marrow failure (BMF) by 12 years of age.

This is a phase I/II clinical trial to demonstrate the safety and efficacy of performing In Utero Hematopoietic Stem Cell Transplantation (IUHSCT) for fetuses affected by FA. The investigators aim to recruit twelve participants with a prenatal diagnosis of FA. 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. IUHSCT for the fetus takes advantage of the developing fetal immune system to induce tolerance to the transplanted cells without using conditioning or immunosuppression.

The investigators hope to demonstrate that it is safe and effective to perform IUHSCT in fetuses diagnosed with FA. 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.

Keywords

Fanconi Anemia, Anemia, Hypoplastic, Congenital, Congenital Bone Marrow Failure Syndromes, Bone Marrow Failure Disorders, Genetic Diseases, Inborn, Congenital, Hereditary, and Neonatal Diseases and Abnormalities, DNA Repair-Deficiency Disorders, Cancer Predisposition Syndrome, cell transplants, grafts, stem cells, bone marrow, prenatal, Inborn Genetic Diseases, IUHSCT for FA-affected fetuses

Eligibility

You can join if…

  • Male or female fetuses from 190/7 - 280/7 weeks gestational age at time of transplant.
  • Diagnosed with FA by either chorionic villus sampling (CVS), or amniocentesis, or cordocentesis with abnormal fetal chromosomal breakage studies and/or FANC gene mutations when combined with at least one of the following: 1) abnormal chromosomal breakage result consistent with an FA diagnosis, 2) family history of a 1st degree relative with confirmed FA, or 3) congenital anomalies consistent with the diagnosis of FA on fetal ultrasound.
  • Parents must consent to fetal autopsy in the event of a fetal demise.
  • Adequate bone marrow harvest from maternal participant is a condition for inclusion.

You CAN'T join if...

  • Fetal Participant Exclusion Criteria: Major anatomic or genetic anomalies that contributes a significant morbidity or mortality risk, and/or echocardiogram or ultrasound findings that indicate a high risk of fetal demise after fetal intervention. Fetuses with a normal chromosomal breakage study that determines they are likely FA negative.
  • Maternal Subject Exclusion Criteria: Maternal participants will be excluded if they have one or more morbidities that would preclude bone marrow harvest and fetal intervention including, but not limited to, morbid obesity with a body mass index greater than 40, significant maternal cardiac disease, mirror syndrome, clinically symptomatic maternal anemia, Preterm premature rupture of membranes (PPROM), Active Preterm labor (PTL), opioid use disorder, current use of anticoagulants.

Locations

  • UCSF
    San Francisco California 94143 United States
  • Stanford University
    Stanford California 94305 United States

Lead Scientist at UCSF

  • Tippi MacKenzie, MD
    Tippi MacKenzie is a pediatric and fetal surgeon who is focused on developing better ways to diagnose and treat genetic diseases before birth. She leads a translational research lab examining the unique biology between the mother and her fetus, with the idea that pregnancy complications such as preterm labor arise from a breakdown in maternal-fetal tolerance.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Agnieszka Czechowicz
ID
NCT07408583
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 12 study participants
Last Updated