Prenatal Transplantation for Fetuses With Fanconi Anemia

Phase 2Not Yet RecruitingNCT07408583

Agnieszka Czechowicz12 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female fetuses from 19\^0/7 - 28\^0/7 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. Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

Number of Maternal Participants with Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v6.0.

Number of maternal participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v6.0.

Time frame: From day of treatment to final maternal study visit (30 +/- 15 days after delivery).

Number of Maternal Participants with Serious Adverse Events (SAEs) as Assessed by CTCAE v6.0.

Number of maternal participants with serious adverse events (SAEs) as assessed by CTCAE v6.0.

Time frame: From day of treatment to final maternal study visit (30 +/- 15 days after delivery).

Number of Fetal Participants with Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v6.0.

Number of fetal participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v6.0.

Time frame: From day of treatment to child's final study visit (24 months after birth).

Number of Fetal Participants with Serious Adverse Events (SAEs) as Assessed by CTCAE v6.0.

Number of fetal participants with serious adverse events (SAEs) as assessed by CTCAE v6.0.