Stem Cell Transplant for Sickle Cell Disease

Overseen By Anna B. Pawlowska, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Hydroxyurea

Must not be taking: Investigational agents

Disqualifiers: Uncontrolled illness, Active malignancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for people with sickle cell disease, focusing on the safety of a stem cell transplant from a half-matched family donor. The goal is to make stem cell transplants more accessible by using related donors who are not a perfect match and to reduce treatment toxicity. This approach may benefit individuals with sickle cell anemia who have experienced serious complications such as strokes, severe pain crises, or acute chest syndrome. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any other investigational agents or concurrent biological, chemotherapy, or radiation therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any other investigational drugs or treatments like chemotherapy or radiation therapy while participating.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the safety of haploidentical stem cell transplantation (SCT) for sickle cell disease has greatly improved. Studies have found that this treatment can potentially cure patients. Previously, concerns existed about side effects like graft-versus-host disease (GVHD), which occurs when donor cells attack the patient's body. However, using bone marrow instead of blood from the donor's bloodstream has reduced this risk.

While the treatment aims to be safe, it's important to note that this is an early-stage trial. The main focus is on assessing safety and possible side effects. Prospective participants should remember that early-stage trials are the first step in testing new treatments in humans. They usually involve fewer participants to closely monitor safety and any adverse reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Hematopoietic stem cell transplantation (HSCT) is unique because it offers a potential cure for sickle cell disease by directly addressing the root cause of the condition. Unlike standard treatments, which typically focus on managing symptoms and preventing complications, HSCT involves replacing the patient's defective blood-forming stem cells with healthy ones from a donor. This approach aims to eliminate the production of sickle-shaped red blood cells altogether. Researchers are particularly excited about haploidentical stem cell transplantation, as it allows for a broader range of donor matches, potentially making this curative option accessible to more patients.

What evidence suggests that this treatment might be an effective treatment for sickle cell disease?

Research has shown that haploidentical transplantation, a type of stem cell transplant under study in this trial, could be a promising treatment for sickle cell disease. Studies have found significant improvements in the safety of this transplant, making it a potential cure. In a recent study, 94% of patients who received this treatment were alive after two years, indicating that most lived longer without major issues. This method aims to increase the number of possible donors, allowing more people to benefit from the treatment. ^{1 2 3 4 6}

Who Is on the Research Team?

Anna Pawlowska, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients aged 1-30 with sickle cell anemia who have had severe symptoms like stroke, acute chest syndrome, or frequent pain crises despite treatment. They must not be pregnant, agree to use contraception, and have a half-matched (haploidentical) family donor because no fully matched donor is available.

Inclusion Criteria

I have sickle cell anemia with more than 60% Hgb S.

I have had a stroke or a lasting neurological issue, or my brain blood flow speed is high.

I've had one or more acute chest syndrome episodes in the last 2 years despite treatment.

Exclusion Criteria

Pregnant women are excluded from this study

I do not have any active cancer except for non-melanoma skin cancers.

I have had a stem cell transplant from myself or a donor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Immunosuppressive Therapy

Participants receive 2 cycles of Fludarabine and Dexamethasone for 5 days each cycle

2 weeks

Conditioning Regimen

Participants undergo conditioning with rATG, Fludarabine, and Busulfan

2 weeks

Haploidentical Stem Cell Transplantation

Participants receive a haploidentical hematopoietic stem cell transplant

1 week

Follow-up

Participants are monitored for safety and effectiveness after transplantation

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Hematopoietic stem cell transplantation

Trial Overview The study tests a new approach using two cycles of drugs to suppress the immune system before receiving stem cells from a half-matched family donor. The goal is to safely expand the pool of donors and achieve consistent results without causing harm.

How Is the Trial Designed?

Group I: Haploidentical stem cell transplantation Experimental Treatment 1 Intervention

Hematopoietic stem cell transplantation is already approved in United States, European Union for the following indications:

Approved in United States as Allogeneic stem cell transplant for:

• Acute leukemia
• Adrenoleukodystrophy
• Aplastic anemia
• Bone marrow failure syndromes
• Chronic leukemia
• Hemoglobinopathies
• Hodgkin's lymphoma
• Immune deficiencies
• Inborn errors of metabolism
• Multiple myeloma
• Myelodysplastic syndromes
• Neuroblastoma
• Non-Hodgkin's lymphoma
• Plasma cell disorders
• POEMS syndrome
• Primary amyloidosis
• Sickle cell disease

Approved in European Union as Allogeneic stem cell transplant for:

• Acute leukemia
• Adrenoleukodystrophy
• Aplastic anemia
• Bone marrow failure syndromes
• Chronic leukemia
• Hemoglobinopathies
• Hodgkin's lymphoma
• Immune deficiencies
• Inborn errors of metabolism
• Multiple myeloma
• Myelodysplastic syndromes
• Neuroblastoma
• Non-Hodgkin's lymphoma
• Plasma cell disorders
• POEMS syndrome
• Primary amyloidosis
• Sickle cell disease

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Published Research Related to This Trial

Allogeneic hematopoietic stem-cell transplantation is currently the only curative treatment for sickle cell disease and has been increasingly accepted as a viable option, particularly for severe cases.

Recent advancements aim to improve the accessibility and safety of stem-cell transplantation for sickle cell disease by exploring new conditioning methods and supportive care, moving away from strict adherence to traditional transplantation principles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem-cell transplantation for sickle cell disease: current evidence and opinions. Shenoy, S.[2022]

In a study of 36 patients with sickle cell disease undergoing nonmyeloablative HLA-matched stem cell transplantation, 28% had pre-existing HLA class I antibodies, which led to increased platelet transfusion requirements post-transplant.

Patients with RBC alloantibodies required more red blood cell transfusions and showed significantly lower donor T cell chimerism at one year, indicating that pre-existing RBC alloimmunization may negatively impact long-term engraftment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of pre-existing HLA and red blood cell antibodies on transfusion support and engraftment in sickle cell disease after nonmyeloablative hematopoietic stem cell transplantation from HLA-matched sibling donors: A prospective, single-center, observational study. Nickel, RS., Flegel, WA., Adams, SD., et al.[2022]

A nonmyeloablative bone marrow transplantation approach using related and HLA-haploidentical donors has been developed for sickle cell disease, showing a low risk of complications and allowing for a broader donor pool.

In a study of 17 patients, 11 achieved durable engraftment, with 10 patients remaining asymptomatic and only one case of mild acute graft-versus-host disease, indicating the treatment's safety and potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Bolaños-Meade, J., Fuchs, EJ., Luznik, L., et al.[2022]

In a study of 27 children with the Black African variant of sickle cell anemia who underwent allogeneic hematopoietic stem cell transplantation, all patients achieved sustained engraftment and remained free of sickle cell-related complications post-transplant.

The transplantation led to a normalization of erythroid populations in the bone marrow, indicating improved erythroid maturation and reduced apoptosis, which suggests a promising curative effect for sickle cell anemia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of intramedullary apoptosis after stem cell transplantation in black african variant of pediatric sickle cell anemia. Isgrò, A., Sodani, P., Marziali, M., et al.[2021]

A novel nonmyeloablative HLA-haploidentical peripheral blood stem cell transplantation (PBSCT) approach showed promising results in 21 patients with sickle cell disease (SCD), with an overall survival rate of 87% and no transplant-related mortality.

The use of posttransplant cyclophosphamide (PT-Cy) significantly improved engraftment rates from 33% to 83% across three cohorts, while effectively preventing severe graft-versus-host disease (GVHD), indicating a safer and more effective treatment option for patients with severe organ damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclophosphamide improves engraftment in patients with SCD and severe organ damage who undergo haploidentical PBSCT. Fitzhugh, CD., Hsieh, MM., Taylor, T., et al.[2019]

Hematopoietic cell transplantation can potentially cure sickle cell anemia, but it carries a 5-10% risk of mortality, highlighting the need for careful consideration of risks versus benefits.

Among 147 patients who received allografts for sickle cell disease, those who achieved stable donor-host hematopoietic chimerism experienced significant clinical improvements, suggesting that strategies to promote stable chimerism could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell transplantation for sickle cell disease: can we reduce the toxicity? Fixler, J., Vichinsky, E., Walters, MC.[2007]

Allogeneic hematopoietic stem cell transplantation (HSCT) is a critical treatment option for various diseases, but it carries risks of morbidity and mortality, highlighting the importance of donor safety during the stem cell donation process.

Bone marrow donation is a well-established and generally safe procedure, with a low incidence of serious adverse events (only 1 fatal event reported among 27,770 donations), and the most common side effects being pain and fatigue, indicating that careful donor selection is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of bone marrow stem cell donation: a review. Bosi, A., Bartolozzi, B.[2010]

In a study of 29 sickle cell disease patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), T-cell neogenesis was initially normal but declined post-transplant, fully restoring to healthy levels by one year, while B-cell neogenesis remained elevated throughout follow-up.

The presence of increased IL-10-producing B-regulatory cells after transplantation suggests a potential improvement in immune regulation and homeostasis, which may be beneficial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation resets T- and B-cell compartments in sickle cell disease patients. Jarduli-Maciel, LR., de Azevedo, JTC., Clave, E., et al.[2022]

In a study of 1680 related donors of hematopoietic cell transplants, only 12 severe adverse events (SAEs) were reported, indicating a low incidence rate of 0.71%, with no fatalities among donors.

Most SAEs occurred in donors who were either overweight or obese, and some had pre-existing medical conditions that could have made them ineligible for donation, highlighting the importance of careful donor screening and counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Adverse Events in Related Donors: A Report from the Related Donor Safe Study. Seftel, MD., Chitphakdithai, P., Miller, JP., et al.[2023]

Hematopoietic stem cell transplantation is currently the only curative treatment for severe sickle cell anemia, with over 85% of 250 patients worldwide surviving free of the disease and enjoying a good quality of life.

The main challenge in this treatment is finding an HLA-identical sibling donor, and while graft-versus-host disease (GvHD) is a significant complication, the use of myeloablative conditioning and immunosuppressive medication helps manage this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hematopoietic stem cell transplantation for severe sickle cell disease]. Klein, A., Brachet, C., Azzi, N., et al.[2006]

Bone marrow transplantation has shown potential as a treatment for sickle cell anemia, as demonstrated by an 8-year-old girl who successfully transitioned from sickle cell anemia to the donor's sickle cell trait after the procedure.

Despite the promising results, the use of bone marrow transplantation for sickle cell anemia is limited by significant immunological complications, particularly graft-vs.-host disease, which poses challenges for broader application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation in the treatment of sickle cell anemia. Johnson, FL.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34537420/

Haploidentical Allogeneic Stem Cell Transplantation in ... We conclude that the safety of haploidentical SCT in SCD patients has improved significantly, and that this should be considered as a curative option in ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S266663672101232X

Haploidentical Allogeneic Stem Cell Transplantation in ... We conclude that the safety of haploidentical SCT in SCD patients has improved significantly, and that this should be considered as a curative option in ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/4/877/526317/Is-allogeneic-transplantation-for-sickle-cell

Is allogeneic transplantation for sickle cell disease still ... Five participants died from infectious complications for an overall 2-year event-free survival (EFS) of 83% and an overall survival (OS) of 94%.

4. astctjournal.org astctjournal.org/article/S2666-6367(25)01447-2/fulltext

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... Recent advancements have improved the overall outcomes of allo-HSCT in SCD. ABSTRACT. Sickle cell disease (SCD) is a life-threatening hemolytic ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/16078454.2022.2163357

A systematic review comparing allogeneic hematopoietic ... Allogeneic hematopoietic stem cell transplant (HSCT) and gene therapy (GT) are two potentially curative approaches for sickle cell disease (SCD), but they have ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11960486/

Clinical Outcomes Among Patients With Sickle Cell ... The purpose of this study is to synthesize evidence on disease-specific outcomes in patients with sickle cell disease (SCD) or transfusion-dependent beta- ...