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| Name | Class |
|---|---|
| University of California, San Francisco | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention - in utero hematopoietic stem cell transplantation | Experimental | Single dose in utero hematopoietic stem cell transplantation (IUHSCT) in fetuses with Fanconi anemia during 19 - 28 weeks gestation. 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.). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IUHSCT for FA-affected fetuses | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | From day of treatment to child's final study visit (24 months after birth). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Agnieszka Czechowicz, MD, PhD | Contact | 650-497-2218 | bmf@stanfordchildrens.org | |
| Yair Blumenfeld, MD | Contact | 650-725-5720 | mfmresearch@stanford.edu |
| Name | Affiliation | Role |
|---|---|---|
| Yair Blumenfeld, MD | Stanford University | Principal Investigator |
| Tippi MacKenzie, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco | San Francisco | California | 94143 | United States | ||
| Stanford University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38991119 | Background | Swartzrock L, Dib C, Denis M, Willner H, Ho K, Haslett E, Han J, Pan W, Byrne-Steele M, Brown B, Krampf MR, Girsen A, Blumenfeld YJ, El-Sayed YY, Roncarolo MG, MacKenzie TC, Czechowicz AD. In utero hematopoietic stem cell transplantation for Fanconi anemia. Blood Adv. 2024 Sep 10;8(17):4554-4558. doi: 10.1182/bloodadvances.2023011894. No abstract available. | |
| 37906519 |
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| Stanford |
| California |
| 94305 |
| United States |
| Dave A, Liu S, Riley JS, Bose S, Luks V, Berkowitz C, Menon P, Jung S, Li H, Kurre P, Peranteau WH. In utero hematopoietic cell transplantation leads to sustained engraftment in a mouse model of Fanconi anemia. Blood Adv. 2024 Feb 13;8(3):624-628. doi: 10.1182/bloodadvances.2023010354. No abstract available. |
| 41711672 | Background | Lum T, Lee C, MacKenzie T, Lianoglou B, Czechowicz A. Attitudes Toward Prenatal Interventions in the Fanconi Anemia Community. Prenat Diagn. 2026 Feb 19. doi: 10.1002/pd.70077. Online ahead of print. |
| ID | Term |
|---|---|
| D005199 | Fanconi Anemia |
| D029502 | Anemia, Hypoplastic, Congenital |
| D000080984 | Congenital Bone Marrow Failure Syndromes |
| D000080983 | Bone Marrow Failure Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D049914 | DNA Repair-Deficiency Disorders |
| ID | Term |
|---|---|
| D000741 | Anemia, Aplastic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D007232 | Infant, Newborn, Diseases |
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