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

11 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Hematopoietic stem cell transplantation for Sickle Cell Disease?

Research shows that hematopoietic stem cell transplantation is the only treatment that can cure sickle cell disease, with more than 85% of patients surviving free of the disease and having a good quality of life. This treatment has been effective in both children and adults, although finding a suitable donor can be challenging. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Hematopoietic stem cell transplantation for Sickle Cell Disease?

Research shows that hematopoietic stem cell transplantation is currently the only curative treatment for sickle cell disease, with more than 85% of patients surviving free of the disease and having a good quality of life. Additionally, nonmyeloablative approaches have expanded donor options and reduced complications, making the treatment more accessible and effective for many patients. ^{2 3 4 5 6}

Is stem cell transplantation safe for humans?

Stem cell transplantation, including bone marrow transplants, has been performed for over 30 years and is generally considered safe, though it carries some risks. For sickle cell disease, there is a 5-10% risk of death associated with the procedure. Common side effects for donors include pain and fatigue, with serious adverse events being rare. ^{2 3 7 8 9}

Is stem cell transplantation safe for humans?

Stem cell transplantation, including bone marrow transplants, has been performed for over 30 years and is generally considered safe, though it carries some risks. For sickle cell disease, there is a 5-10% risk of death associated with the procedure. Common side effects for donors include pain and fatigue, with serious adverse events being rare. ^{2 3 7 8 9}

How is the treatment of hematopoietic stem cell transplantation unique for sickle cell disease?

Hematopoietic stem cell transplantation is unique for sickle cell disease because it is currently the only treatment that can cure the condition, unlike other treatments that only manage symptoms. This therapy involves replacing the patient's faulty blood-forming stem cells with healthy ones from a donor, which can eliminate the disease entirely. ^{1 2 3 10 11}

How is hematopoietic stem cell transplantation different from other treatments for sickle cell disease?

Hematopoietic stem cell transplantation is unique because it is currently the only treatment that can cure sickle cell disease, unlike other treatments that only manage symptoms. This procedure involves replacing the patient's bone marrow with healthy stem cells from a donor, which can eliminate the disease entirely. ^{1 2 3 10 11}

What is the purpose of this trial?

This is a study to evaluate the safety and toxicity of a treatment regimen consisting of 2 cycles of pre-transplant immunosuppressive therapy followed by myeloablative preparative regimen and allogeneic hematopoietic stem cell transplantation from a haploidentical donor in patients with sickle cell disease. The overall goal of this study is to expand the donor pool for hematopoietic stem cell transplantation in sickle cell disease using haploidentical donors, and to develop a non-toxic, myeloablative regimen, with the goal of achieving a consistent donor chimerism utilizing pre-transplant immunosuppressive therapy.

Research Team

Anna Pawlowska, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Reduction of intramedullary apoptosis after stem cell transplantation in black african variant of pediatric sickle cell anemia. [2021]

2. England pubmed.ncbi.nlm.nih.gov

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

3. England 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. [2022]

5. Belgium pubmed.ncbi.nlm.nih.gov

[Hematopoietic stem cell transplantation for severe sickle cell disease]. [2006]

6. United States pubmed.ncbi.nlm.nih.gov

Cyclophosphamide improves engraftment in patients with SCD and severe organ damage who undergo haploidentical PBSCT. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Stem cell transplantation for sickle cell disease: can we reduce the toxicity? [2007]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of bone marrow stem cell donation: a review. [2010]

9. United States pubmed.ncbi.nlm.nih.gov

Serious Adverse Events in Related Donors: A Report from the Related Donor Safe Study. [2023]

10. Australia pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation resets T- and B-cell compartments in sickle cell disease patients. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

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