What side effects are associated with this type of intervention?

Common treatments for Sickle Cell Disease (SCD) include hydroxyurea, chronic transfusion therapy, and bone marrow transplantation. Hydroxyurea can cause bone marrow suppression, leading to lower white blood cell and platelet counts, and potential infertility in men. Chronic transfusion therapy may result in iron overload, alloimmunization, and transfusion reactions. Bone marrow transplantation, including haploidentical transplantation, carries risks of graft-versus-host disease (GVHD), infections due to immunosuppression, and transplant rejection. These treatments aim to manage SCD symptoms and complications but come with significant risks that need to be carefully managed.

What prior FDA approvals exist?

The FDA has approved several treatments for Sickle Cell Disease (SCD), including hydroxyurea, which reduces complications and increases life expectancy, and voxelotor, which improves hemoglobin levels. While bone marrow transplantation, including haploidentical transplants, is a potential curative option for SCD, it is not yet in routine use and remains under investigation. Other FDA-approved treatments focus on managing symptoms and preventing complications rather than curing the disease.

What other types of research exist?

Promising, novel alternatives to Haploidentical Bone Marrow Transplantation for Sickle Cell Disease patients include: 1) Hydroxyurea, which is recommended as the first-line therapy due to its efficacy in reducing vaso-occlusive pain and other complications, and improving survival. 2) Chronic transfusions, which can help manage and prevent complications such as stroke. 3) New medications that modify the pathogenesis of SCD-associated vaso-occlusion, which are emerging as effective options. These alternatives should be discussed with a healthcare provider to determine the best individualized treatment plan.

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Chemotherapy

Haploidentical Bone Marrow Transplant for Sickle Cell Disease

Q: What is the mechanism of action of this treatment?

The most common treatments for Sickle Cell Disease (SCD) include hydroxyurea, red blood cell transfusions, and hematopoietic stem cell transplantation (HSCT). Hydroxyurea works by increasing fetal hemoglobin (HbF) levels, which reduces the sickling of red blood cells and decreases vaso-occlusive episodes. Red blood cell transfusions help by increasing the number of normal red blood cells, thereby reducing the proportion of sickled cells and preventing complications such as stroke. HSCT, including haploidentical bone marrow transplantation, involves replacing defective bone marrow with healthy donor marrow, potentially curing SCD by enabling the production of normal red blood cells. These treatments are crucial for SCD patients as they aim to alleviate pain, prevent severe complications, and improve overall quality of life and survival.

Phase 2

Waitlist Available

Research Sponsored by Medical College of Wisconsin

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Umbilical cord blood or peripheral blood stem cell donors will not be accepted.

Hepatic function: Serum conjugated (direct) bilirubin < 2x upper limit of normal for age, ALT and AST < 5x upper limit of normal, and liver MRI for participants with specific transfusion history

Must not have

Had an Encephaloduroarteriosynangiosis (EDAS) procedure in the 6 months prior to enrollment

Uncontrolled autoimmune disease requiring active medical management

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 and 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a special type of bone marrow transplant for children and adults with severe sickle cell disease. It uses medications to prepare the body and a donor to replace defective bone marrow. The goal is to improve survival without major complications. Bone marrow transplantation is currently the only curative therapy for sickle cell disease, but it is limited by side effects and finding suitable donors.

Who is the study for?

This trial is for children (5-14.99 years) and adults (15-45.99 years) with severe sickle cell disease who have a family member willing to donate bone marrow that partially matches their HLA type. Participants must be in good physical condition, not pregnant or breastfeeding, and agree to use contraception if of childbearing potential.

What is being tested?

The study tests the effectiveness and safety of haploidentical bone marrow transplantation in treating severe sickle cell disease. It includes medications like Hydroxyurea, Rabbit-ATG, Thiotepa, Fludarabine, Cyclophosphamide plus Total Body Irradiation and Mesna as part of the treatment process.

What are the potential side effects?

Possible side effects include immune reactions from the transplant leading to graft-versus-host disease, infections due to weakened immunity post-transplantation, organ damage from chemotherapy drugs or radiation therapy used before transplantation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am not using umbilical cord or peripheral blood stem cells for my treatment.

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My liver tests are within the required range and I may need a liver MRI due to my transfusion history.

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I have a family member who matches my HLA type and is willing to donate bone marrow.

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My kidney function is within the normal range for my age.

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I can care for myself but may need occasional help.

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My heart's pumping ability is within the required range.

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My oxygen levels are good and my lungs work well enough to breathe properly.

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I am between 5 and 14 years old.

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I can do most activities, my heart and lungs work well enough for treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I had a surgery to improve brain blood flow within the last 6 months.

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I am actively being treated for an autoimmune disease that is not under control.

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I am not pregnant or breastfeeding.

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I have had a bone marrow or stem cell transplant.

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I have a sibling who matches my HLA type and can donate bone marrow.

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My body has antibodies against a donor organ.

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I agree to use two forms of birth control or practice true abstinence.

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I am a male and agree to use effective contraception or practice abstinence.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 and 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 and 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Two-Year Post-Transplant Event Free Survival (EFS)

Secondary study objectives

Chimerism

Disease Recurrence

Graft Rejection

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Haploidentical TransplantationExperimental Treatment8 Interventions

A conditioning regimen with Hydroxyurea, rabbit-ATG, Thiotepa, Fludarabine, Cyclophosphamide, Total Body Irradiation, and Mesna will be administered prior to Haploidentical Bone Marrow Transplantation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Haploidentical Bone Marrow Transplantation

2008

Completed Phase 2

~60

Hydroxyurea

2006

Completed Phase 4

~3490

Thiotepa

2008

Completed Phase 3

~2120

Fludarabine

2012

Completed Phase 4

~1860

Cyclophosphamide

2010

Completed Phase 4

~2310

Total Body Irradiation

2006

Completed Phase 3

~820

Mesna

2003

Completed Phase 2

~1380

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Sickle Cell Disease (SCD) include hydroxyurea, red blood cell transfusions, and hematopoietic stem cell transplantation (HSCT). Hydroxyurea works by increasing fetal hemoglobin (HbF) levels, which reduces the sickling of red blood cells and decreases vaso-occlusive episodes. Red blood cell transfusions help by increasing the number of normal red blood cells, thereby reducing the proportion of sickled cells and preventing complications such as stroke. HSCT, including haploidentical bone marrow transplantation, involves replacing defective bone marrow with healthy donor marrow, potentially curing SCD by enabling the production of normal red blood cells. These treatments are crucial for SCD patients as they aim to alleviate pain, prevent severe complications, and improve overall quality of life and survival.

Hematopoietic stem cell transplantation for children with sickle cell disease.