In Utero Stem Cell Transplant for Thalassemia

Overseen By Tippi Mackenzie, MD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Francisco

Disqualifiers: Morbid obesity, Cardiac disease, Mirror syndrome, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new stem cell treatment for unborn babies diagnosed with a severe blood disorder called alpha-thalassemia major. The researchers aim to determine the safety of administering stem cells directly to the fetus when a blood transfusion is already needed in the womb. This trial suits fetuses between 18 and 26 weeks of gestation, diagnosed with alpha-thalassemia major, and already scheduled for an in-utero transfusion. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that in utero hematopoietic stem cell transplantation is safe for fetuses with alpha-thalassemia major?

Research has shown that in utero hematopoietic stem cell transplantation (IUHSCT) is safe and well-tolerated for unborn babies with alpha-thalassemia major. In two cases, researchers safely administered this treatment using stem cells from the mother. This method is considered safer than traditional stem cell transplants performed after birth. However, this treatment remains in the early stages of research, so information on long-term effects is limited. Participants in this trial will receive close monitoring to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for thalassemia?

Most treatments for thalassemia involve regular blood transfusions and iron chelation therapy to manage symptoms and prevent complications. However, the in utero stem cell transplant is unique because it aims to treat the condition before birth by delivering maternal stem cells directly into the fetus. This approach could potentially correct the genetic defect that causes thalassemia, reducing or even eliminating the need for lifelong blood transfusions. Researchers are excited about this treatment because it offers a chance to address the disease at its root, potentially improving quality of life dramatically for affected individuals from the very start.

What evidence suggests that in utero hematopoietic stem cell transplantation might be an effective treatment for alpha-thalassemia?

Research has shown that administering stem cells to a fetus before birth might help treat blood disorders like thalassemias. Previous studies have produced positive results, particularly in severe cases of alpha-thalassemia major. In this trial, participants will undergo in utero hematopoietic stem cell transplantation, which involves providing stem cells to the unborn baby. This procedure may enhance blood cell production. Early findings suggest that this approach could improve the condition by addressing the root cause before birth. While the main focus is on safety, this treatment offers hope for effectively managing the disease. ^{1 3 4 6 7}

Who Is on the Research Team?

Tippi Mackenzie, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for fetuses between 18 to 26 weeks old diagnosed with alpha-thalassemia major, showing signs of anemia or hydrops. Parents must be genetic carriers and agree to in utero treatments and a possible autopsy if the fetus doesn't survive. The mother must be healthy enough for bone marrow harvest without conditions like obesity or heart disease.

Inclusion Criteria

My bone marrow harvest is sufficient for the study's needs.

Parents must consent to fetal autopsy in the event of a fetal demise

My unborn child has alpha-thalassemia major and we've chosen in utero treatment.

Exclusion Criteria

I do not have conditions like severe obesity, heart disease, or anemia that would prevent safe surgery.

My unborn child does not have major health issues unrelated to thalassemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

In Utero Treatment

In utero hematopoietic stem cell transplantation performed at the time of in utero transfusion of red blood cells

Immediate procedure

1 visit (in-person)

Postnatal Follow-up

Participants are monitored for successful engraftment and safety, including chimerism and survival

1 year

Weekly visits for the first 4 weeks, then monthly visits for 1 year

Long-term Follow-up

Monitoring of long-term outcomes and stability of engraftment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• In Utero Hematopoietic Stem Cell Transplantation

Trial Overview The trial tests the safety of giving hematopoietic stem cells (cells that can form blood cells) to a fetus during an existing treatment where they get red blood cell transfusions inside the womb.

How Is the Trial Designed?

Group I: in utero hematopoietic stem cell transplantation Experimental Treatment 1 Intervention

Perform in utero hematopoietic stem cell transplantation at the time of intrauterine transplantation in fetuses with alpha-thalassemia major. 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.). Stem cells will be administered immediately before the red blood cells intravenously via the umbilical vein during the clinically indicated IUT. All participants will receive one dose of stem cells but may receive additional transfusions as clinically indicated.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02986698

In Utero Hematopoietic Stem Cell Transplantation for Alpha ... This is a phase 1 clinical trial to demonstrate the safety, feasibility and efficacy of performing in utero stem cell transplantation on fetuses affected with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4290536/

In utero hematopoietic cell transplantation for ... In utero hematopoietic cell transplantation has excellent potential to treat common hemoglobinopathies such as sickle cell disease and thalassemias. In ...

3. fetus.ucsf.edu fetus.ucsf.edu/intrauterine-therapy-alpha-thalassemia-major/

Intrauterine Therapy for Alpha Thalassemia Major Phase 1 clinical trial for alpha thalassemia major, using transplanted maternal stem cells to the fetus at the same time as a planned in-utero transfustion.

4. ashpublications.org ashpublications.org/hematology/article-abstract/2021/1/592/483019

Advances in the management of α-thalassemia major In this review, we discuss the experience with postnatal stem cell transplantation in patients with ATM, as well as the ongoing phase 1 clinical ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9860434/

The impact of in utero transfusions on perinatal outcomes ... Fetuses with ATM who receive ≥2 IUTs have resolution of hydrops with near-term birth and a short hospital stay. Children with ATM who received ≥2 IUTs have ...

6. ashpublications.org ashpublications.org/ashclinicalnews/news/5450/In-Utero-Hematopoietic-Cell-Transplantation-Safe

In Utero Hematopoietic Cell Transplantation Safe in Fetuses ... In utero hematopoietic cell transplantation (IUHCT) with maternal cells was safe in two fetuses with alpha thalassemia major (ATM), according ...

7. cirm.ca.gov cirm.ca.gov/our-progress/awards/utero-hematopoietic-stem-cell-transplantation-treatment-fetuses-alpha-thalassemia-major/

In Utero Hematopoietic Stem Cell Transplantation For The ... Alpha thalassemia major is almost always fatal in utero, and rare survivors need costly and morbid chronic care. There is an unmet clinical need to develop a ...