Anemia, Hypoplastic, Congenital, Bone Marrow Failure Disorders, Cancer Predisposition Syndrome, Congenital Bone Marrow Failure Syndromes, Congenital, Hereditary, and Neonatal Diseases and Abnormalities, DNA Repair-Deficiency Disorders, Fanconi Anemia, Genetic Diseases, Inborn
Conditions
Keywords
cell transplants, grafts, stem cells, bone marrow, Fanconi anemia, prenatal
Brief summary
The investigators aim to evaluate the safety and efficacy of in utero hematopoietic stem cell transplantation (IUHSCT) for the treatment of fetuses diagnosed with Fanconi anemia (FA) during pregnancy.
Detailed description
Fanconi Anemia (FA) is a genetic disorder known to shorten the lifespans of those diagnosed due to inherited chromosomal fragility that leads to hematopoietic failure (cytopenia, 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 investigate the safety and efficacy of performing in utero hematopoietic stem cell transplantation (IUHSCT) for fetuses diagnosed with FA during pregnancy. The investigators aim to recruit twelve participants with a prenatal diagnosis of FA. Participants will undergo bone marrow harvest followed by an ultrasound guided in utero infusion of maternal stem cells. Transplanting maternal cells into the fetus takes advantage of the immature fetal immune system and existing maternal-fetal tolerance during pregnancy to enable stem transplantation without use of any conditioning or immunosuppression. The investigators intend 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 and correction of the DNA-repair deficiency in the blood and bone marrow. This procedure hopes to prevent the need for a future bone marrow transplant later in life, or if one remains necessary then it hopes that conditioning and immune suppression will not be required when using maternal stem cells due to persistant maternal tolerance.
Interventions
BIOLOGICALIUHSCT for FA-affected fetuses
Single-dose IUHSCT Administration of Semi-allogeneic, Related, Maternal Bone Marrow-Derived, Miltenyi CliniMACS Plus Enriched CD34+ Hematopoietic Stem Cells Administered in Utero via fetal injection during 19 - 28 weeks gestation.
Sponsors
Agnieszka Czechowicz
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Maternal Participants with Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v6.0. | From day of treatment to final maternal study visit (30 +/- 15 days after delivery). | Number of maternal participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v6.0. |
| Number of Maternal Participants with Serious Adverse Events (SAEs) as Assessed by CTCAE v6.0. | 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 Fetal Participants with Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v6.0. | From day of treatment to child's final study visit (24 months after birth). | Number of fetal participants with treatment-emergent adverse events (TEAEs) as assessed by CTCAE v6.0. |
| Number of Fetal Participants with Serious Adverse Events (SAEs) as Assessed by CTCAE v6.0. | 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. |
Countries
United States
Contacts
CONTACTAgnieszka Czechowicz, MD, PhD
CONTACTYair Blumenfeld, MD
PRINCIPAL_INVESTIGATORYair Blumenfeld, MD
Stanford University
PRINCIPAL_INVESTIGATORTippi MacKenzie, MD
University of California, San Francisco
Outcome results
None listed