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In-utero Hematopoietic Stem Cell Transplantation for the Treatment of Fetuses With Bart's Hydrops Fetalis Syndrome

Primary Purpose

Haemoglobin Barts Hydrops

Status
Recruiting
Phase
Not Applicable
Locations
Hong Kong
Study Type
Interventional
Intervention
in-utero HSCT
Sponsored by
Chinese University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Haemoglobin Barts Hydrops focused on measuring in-utero transplantation, hematopoietic stem cell, Bart's syndrome, hydrops fetalis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Pregnancy before 26 weeks and 0 day of gestational age with a diagnosis of BHFS confirmed by chorionic villus sampling, amniocentesis or cordocentesis; The parents elected to pursue IUT and are willing to undergo subsequent IUT for the remainder of gestation. Exclusion Criteria: A) Fetal subjects: Fetuses having a second major anatomic anomaly (not related to the underlying thalassemia) that contributes a significant morbidity or mortality risk; Fetuses having a genetic or chromosomal abnormalities other than BHFS that contributes a significant morbidity or mortality risk; Echocardiogram or ultrasound findings that indicate a high risk of fetal demise after fetal intervention; Fetuses diagnosed with in-utero death prior to the actual intervention. B) Maternal subjects: Maternal age < 18 years, mentally handicapped or severely ill; Maternal participants having one or more morbidities that would preclude bone marrow or peripheral blood stem cells harvest and fetal intervention including, but not limited to, bleeding disorder, maternal cardiac disease, maternal mirror syndrome, symptomatic maternal anemia, or if they develop preterm premature rupture of membranes or active preterm labor; Unable to understand English or Chinese to give consent.

Sites / Locations

  • The Chinese University of Hong KongRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fetuses with BHFS

Arm Description

Fetuses of pregnant women confirmed with BHFS

Outcomes

Primary Outcome Measures

Rate of maternal complications
Maternal participant tolerance of bone marrow or peripheral blood stem cells harvest with prior granulocyte colony-stimulating factor (G-CSF) administration: - Maternal participant tolerance defined as not requiring interventions for preterm labor, bleeding, infection or prolonged hospitalization. Any side effects or adverse outcome related to the procedure or related medications observed will be well documented.
Rate of survival of fetus
Safety of in utero HSCT 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.

Secondary Outcome Measures

Full Information

First Posted
March 7, 2023
Last Updated
April 10, 2023
Sponsor
Chinese University of Hong Kong
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1. Study Identification

Unique Protocol Identification Number
NCT05797272
Brief Title
In-utero Hematopoietic Stem Cell Transplantation for the Treatment of Fetuses With Bart's Hydrops Fetalis Syndrome
Official Title
Feasibility of In-utero Hematopoietic Stem Cell Transplantation as a Conjunctive Treatment During In-utero Blood Transfusion for Hemoglobin Bart's Hydrops Fetalis Syndrome in Hong Kong
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
September 30, 2027 (Anticipated)
Study Completion Date
September 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective observational pilot study on pregnant women who are diagnosed to have Bart's hydrops fetalis syndrome (BHFS) affected fetuses and opt for continuation of pregnancy will be invited to consider undergoing in-utero hematopoietic stem cell transplantation under a research protocol, aiming to determine whether in-utero hematopoietic stem cell transplantation (HSCT) for fetuses with confirmed BHFS at the time of in-utero transfusion (IUT) of red blood cells could be feasible in Hong Kong. The participants will undergo bone marrow or peripheral blood stem cells harvest and an IUT combined with maternal stem cells.
Detailed Description
Alpha thalassemia major or hemoglobin BHFS is thought to be incompatible of life. A prevalence study conducted in Hong Kong showed 4.6% of the screened population are heterozygous carriers of deletional type alpha thalassemia, who would have 25% risk of conceiving fetuses with BHFS if both couple are carrier. Fetuses with BHFS often develop severe anaemia in utero, feature with cardiomegaly, high peak systolic velocity in middle cerebral artery (MCA PSV), thickened placenta, and eventually hydrops, which can lead to intrauterine fetal demise or early neonatal death; while the mother may also be at risk of maternal mirror syndrome which will cause significant morbidity and even mortality. As a result, when the foetuses are diagnosed with BHFS, most couple will terminate the pregnancy. With the advance of technology, if the couples are both known to be alpha thalassemia carrier (alpha-alpha couples), they may consider pre-implantation genetic diagnosis. However, even though preimplantation genetic testing for monogenic disease (PGT-M) is a mature technique over the decades, it is still technically challenging, requires assisted reproductive technology even if the couple are fertile and relative costly. As a result, most of the alpha-alpha couples still conceive naturally. Prenatal ultrasonic surveillance is usually offered for the couples and prenatal diagnosis is required for genetic analysis to confirm BHFS when there is ultrasound feature of fetal anaemia. Thus, the investigators propose this pilot study to determine whether in-utero hematopoietic stem cell transplantation for fetuses with confirmed alpha thalassemia major at the time of IUT of red blood cells could be feasible in Hong Kong.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Haemoglobin Barts Hydrops
Keywords
in-utero transplantation, hematopoietic stem cell, Bart's syndrome, hydrops fetalis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fetuses with BHFS
Arm Type
Experimental
Arm Description
Fetuses of pregnant women confirmed with BHFS
Intervention Type
Procedure
Intervention Name(s)
in-utero HSCT
Intervention Description
Pregnant women who are diagnosed to have BHFS affected fetuses and opt for continuation of pregnancy will undergo in-utero HSCT.
Primary Outcome Measure Information:
Title
Rate of maternal complications
Description
Maternal participant tolerance of bone marrow or peripheral blood stem cells harvest with prior granulocyte colony-stimulating factor (G-CSF) administration: - Maternal participant tolerance defined as not requiring interventions for preterm labor, bleeding, infection or prolonged hospitalization. Any side effects or adverse outcome related to the procedure or related medications observed will be well documented.
Time Frame
during pregnancy (up to week 40)
Title
Rate of survival of fetus
Description
Safety of in utero HSCT 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
during pregnancy (up to week 40)

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Pregnant women
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pregnancy before 26 weeks and 0 day of gestational age with a diagnosis of BHFS confirmed by chorionic villus sampling, amniocentesis or cordocentesis; The parents elected to pursue IUT and are willing to undergo subsequent IUT for the remainder of gestation. Exclusion Criteria: A) Fetal subjects: Fetuses having a second major anatomic anomaly (not related to the underlying thalassemia) that contributes a significant morbidity or mortality risk; Fetuses having a genetic or chromosomal abnormalities other than BHFS that contributes a significant morbidity or mortality risk; Echocardiogram or ultrasound findings that indicate a high risk of fetal demise after fetal intervention; Fetuses diagnosed with in-utero death prior to the actual intervention. B) Maternal subjects: Maternal age < 18 years, mentally handicapped or severely ill; Maternal participants having one or more morbidities that would preclude bone marrow or peripheral blood stem cells harvest and fetal intervention including, but not limited to, bleeding disorder, maternal cardiac disease, maternal mirror syndrome, symptomatic maternal anemia, or if they develop preterm premature rupture of membranes or active preterm labor; Unable to understand English or Chinese to give consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tak Yeung LEUNG, MD
Phone
852-35052806
Email
tyleung@cuhk.edu.hk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tak Yeung LEUNG, MD
Organizational Affiliation
Chinese University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Chinese University of Hong Kong
City
Sha Tin
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tak Yeung LEUNG, MD
Phone
852-35052806
Email
tyleung@cuhk.edu.hk

12. IPD Sharing Statement

Learn more about this trial

In-utero Hematopoietic Stem Cell Transplantation for the Treatment of Fetuses With Bart's Hydrops Fetalis Syndrome

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