Stem Cell Transplant for Sickle Cell Anemia

Overseen By Emily M Limerick, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Disqualifiers: Uncontrolled infections, Major organ failure, Pregnancy, Secondary malignancies, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help people with sickle cell disease by providing a second stem cell transplant, known as Repeat Peripheral Blood Stem Cell Transplantation. It targets individuals whose disease returned after their first transplant but who still retain some donor cells. The goal is to create more space in the bone marrow to accept new donor cells and potentially cure the disease. Individuals with sickle cell disease and a previous transplant that was not fully effective might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, it focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group.

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.

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

Earlier studies have shown promise for a second stem cell transplant in treating sickle cell disease if it returns after the first transplant. Research suggests that patients tolerate this treatment well.

A large review of similar stem cell transplants found that more than 90% of patients survived the procedure. However, some risks exist. For adults, these procedures can be more challenging, and complications might occur.

In this study, participants receive donor cells from family members, which can help reduce some risks. Overall, while side effects can occur, the treatment has been effective in many cases. It is important for each person to discuss these risks and benefits with their healthcare team before making a decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using repeat peripheral blood stem cell transplantation for sickle cell anemia because it offers a potential cure rather than just symptom management. Unlike standard treatments like blood transfusions and hydroxyurea, which mainly aim to alleviate symptoms, this approach targets the root cause by replacing damaged cells with healthy ones. Additionally, using haploidentical donors and HLA-matched sibling donors expands the pool of potential matches, making stem cell therapy accessible to more patients. This innovative strategy could significantly improve outcomes and quality of life for those suffering from this condition.

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

Research has shown that stem cell transplants can effectively treat sickle cell disease. Studies have found high success rates, with 97-98% of patients surviving and 91% remaining disease-free. In this trial, participants will receive stem cell transplants from either HLA-matched sibling donors or haploidentical donors. If the disease returns, a second transplant may help by allowing more donor cells to grow in the bone marrow. Stem cell transplants work especially well for children and young adults. Although the process can be more challenging for older adults, it still offers hope for many patients. ^{5 6 7 8 9}

Who Is on the Research Team?

Emily M Limerick, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is for people aged 4 and older with sickle cell disease who had a previous stem cell transplant but the disease came back. They need some remaining donor cells in their body, good heart and lung function, and can't be pregnant or breastfeeding. Donors must be relatives, at least 2 years old, without serious health issues.

Inclusion Criteria

Persistent donor chimerism levels

DLCO greater than or equal to 35%

Negative beta-HCG

Exclusion Criteria

I have had cancer before, but it wasn't just skin cancer.

I do not have any major illnesses or organ failures that would make a stem cell transplant impossible.

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-transplant Preparation

Donors take a drug for 5-6 days to prepare for donation; recipients receive drugs to help their body accept donor cells

1-2 weeks

7-8 visits for donors

Transplantation

Recipients receive donor cells and red blood cell transfusions; stay in hospital for about 30 days post-transfusion

4-5 weeks

Inpatient stay for recipients

Initial Follow-up

Recipients have many visits in the first 3 months post-infusion to monitor safety and effectiveness

12 weeks

Multiple visits

Long-term Follow-up

Recipients have visits every 6 months to 1 year for 5 years to monitor long-term outcomes

5 years

Biannual to annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Repeat Peripheral Blood Stem Cell Transplantation

Trial Overview The study tests a second peripheral blood stem cell transplantation using CliniMACS CD34 Reagent to treat sickle cell disease when it returns after an initial transplant. Participants will undergo extensive screening, receive medications to accept new donor cells, and have follow-up visits for up to five years.

How Is the Trial Designed?

Group I: 2 Experimental Treatment 1 Intervention

patients with haploidentical donors

Group II: 1 Experimental Treatment 1 Intervention

patients with HLA-matched sibling donors

Repeat Peripheral Blood Stem Cell Transplantation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as PBSCT for:

• Sickle Cell Disease

Approved in European Union as PBSCT for:

• Sickle Cell Disease
• Leukemia
• Lymphoma
• Multiple Myeloma

Approved in Canada as PBSCT for:

• Sickle Cell Disease
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a safe and effective alternative to allogeneic bone marrow transplantation (allo-BMT), offering faster engraftment for patients, which leads to fewer transfusions and shorter hospital stays.

While allo-PBSCT is well tolerated by donors and provides adequate stem cell numbers, further research is needed to assess the long-term effects of G-CSF on donors and to analyze the durability of hematopoiesis and the incidence of graft versus host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allogeneic peripheral blood stem cell transplantation]. Yamane, T., Hino, M., Ohta, K., et al.[2006]

Allogeneic peripheral blood stem cell transplantation (PBSCT) and bone marrow transplantation (BMT) show similar clinical outcomes, with successful engraftment in 23 PBSCT patients and 24 BMT patients out of 26 and 24 respectively.

However, PBSCT is associated with a significantly higher incidence of chronic graft-versus-host disease (cGVHD) at 56.5% compared to only 3.85% in the BMT group, indicating a potential safety concern despite comparable overall effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of clinical outcome between allogeneic peripheral blood stem cell transplantation and bone marrow transplantation]. Wang, M., Han, M., Feng, S.[2007]

Peripheral blood stem cell transplantation (PBSCT) offers significant advantages over traditional bone marrow transplants, including faster recovery of blood cells, reduced complications, and cost-effectiveness, making it a preferred option for patients with blood cancers.

Recent advancements in stem cell research and techniques, such as cytokine manipulation and gene therapy, are expanding the potential applications of PBSCT beyond cancer treatment to include certain nonmalignant diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral Blood Stem Cells: Transplantation and Beyond. Lie, AK., To, LB.[2019]

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 peripheral blood stem cell transplantation (allo-PBSCT) showed a significantly lower relapse rate (5.7%) compared to autologous PBSCT (auto-PBSCT) which had a relapse rate of 38.9%, indicating better long-term efficacy in treating malignant hematologic diseases.

The study found that allo-PBSCT resulted in a higher disease-free survival rate (69.5%) compared to auto-PBSCT (57.9%), suggesting that allo-PBSCT may be a more effective treatment option for patients with these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Peripheral blood stem cell transplantation for 53 patients with malignant hematologic diseases]. Xie, XS., Wan, DM., Sun, H., et al.[2016]

Autologous peripheral blood stem cell transplantation (PBSCT) is less invasive and does not require anesthesia, leading to faster hematopoietic recovery and fewer complications compared to traditional marrow transplantation.

Preliminary results indicate that PBSCT is as effective as allogeneic bone marrow transplantation for treating relapsed childhood acute lymphoblastic leukemia, suggesting it could be a safe and viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Peripheral blood stem cell transplantation: present status and future prospects]. Takaue, Y.[2006]

In a study of 20 adult patients with poor graft function after allogeneic peripheral blood stem cell transplantation, CD34(+)-selected stem cell boosts significantly improved blood cell counts, with 90% of patients showing increased platelets and leukocytes, and 90% improving hemoglobin levels.

The treatment was found to be safe, with only one case of grade III graft versus host disease reported, indicating that CD34(+)-selected stem cell boosts can effectively enhance recovery from poor graft function with a low risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor graft function can be durably and safely improved by CD34+-selected stem cell boosts after allogeneic unrelated matched or mismatched hematopoietic cell transplantation. Haen, SP., Schumm, M., Faul, C., et al.[2018]

Allogeneic peripheral blood stem cell transplantation (PBSCT) is a safe and effective alternative to bone marrow transplant (BMT), offering faster engraftment which leads to fewer transfusions and shorter hospital stays.

The process of growth factor mobilization and apheresis for PBSCT is well tolerated by donors, but further research is needed to assess long-term side effects and the durability of hematopoiesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic peripheral blood stem cell transplantation: clinical overview and nursing implications. Wagner, ND., Quinones, VW.[2005]

Allogeneic peripheral blood stem cell transplantation (PBSCT) effectively restored blood cell production in a patient with severe aplastic anemia and severe infection, achieving normal neutrophil and platelet counts shortly after treatment.

The combination of cyclophosphamide and total body irradiation for conditioning, along with a sufficient infusion of stem cells, contributed to successful engraftment without any signs of graft versus host disease over a 30-month follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic peripheral blood stem cell transplantation in the treatment of severe aplastic anemia and severe infection. Wan, L., Yan, S., Wang, C., et al.[2004]

In a study of 79 patients receiving peripheral blood stem cell transplants (PBSCT) from unrelated donors, T-cell depletion (TCD) was associated with a higher rate of primary graft-failure (20%) compared to unmanipulated grafts (5%), indicating a potential risk when using TCD to reduce graft-versus-host disease (GvHD).

Patients with standard risk who received their first transplants had significantly better overall survival (60.4%) and disease-free survival (57.2%) compared to high-risk patients, highlighting the importance of risk stratification in transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation of G-CSF mobilized peripheral blood stem cells from unrelated donors: a retrospective analysis. Bornhäuser, M., Theuser, C., Soucek, S., et al.[2021]

In a multicenter phase II study involving 22 patients with standard-risk leukemia, allogeneic peripheral blood stem cell transplantation (allo-PBSCT) resulted in rapid recovery of blood cell counts, with a median of 12 days to achieve neutrophil counts over 500/microl and 16 days for platelet counts over 50,000/microl.

While allo-PBSCT showed no increase in the incidence of acute graft-versus-host disease (GVHD), there was a notable risk of chronic GVHD, affecting 60% of patients, suggesting that while this method is effective, careful monitoring for chronic GVHD is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic peripheral blood stem cell transplantation for standard-risk leukemia. A multicenter pilot study: Japanese experience. Japan Blood Cell Transplantation Study Group. Harada, M., Shinagawa, K., Kawano, T., et al.[2006]

A patient with severe aplastic anemia successfully underwent primary allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an HLA-identical sibling, leading to rapid bone marrow recovery.

The patient has maintained complete remission with normal blood counts for 9 months post-transplant, indicating that allo-PBSCT may be a safe and effective treatment option for severe aplastic anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary transplantation of allogeneic peripheral blood stem cell for severe aplastic anemia. Hsu, HC., Tsai, WH., Lin, JS., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8459571/

Stem cell transplantation in sickle cell disease - PubMed Central UCB transplant outcomes for 485 recipient cases with thalassemia major or SCD was published from the CIBMTR and European Group for Blood and Marrow ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11057353/

Hematopoietic Stem Cell Transplantation in Sickle Cell Disease This review encompasses information on the use of HSCT in patients with SCD, including the indications for HSCT, conditioning regimens, alternative donors, and ...

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Systematic Review/Meta-Analysis on Efficacy of Allogeneic ... This systematic review/meta-analysis demonstrates the efficacy of allo-HCT in sickle cell disease. •. Comparable pooled OS (97% and 98%) and DFS (91% and ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa0904971

Allogeneic Hematopoietic Stem-Cell Transplantation for ... Myeloablative allogeneic hematopoietic stem-cell transplantation is curative in children with sickle cell disease, but in adults the procedure is unduly toxic.

5. ashpublications.org ashpublications.org/blood/article/117/24/6411/22173/Twenty-five-years-of-peripheral-blood-stem-cell

Twenty-five years of peripheral blood stem cell transplantation This historical overview provides a brief insight into the discovery of circulating hematopoietic stem cells in the early 1960s, the development of apheresis ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/229164

Repeat Peripheral Blood Stem Cell Transplantation for ... Objective: To cure people s sickle cell disease by giving a second treatment that makes more room in their bone marrow for donor cells.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5130409/

Allogeneic Stem Cell Transplantation for Sickle Cell Disease In this review we will summarize results from trials of HSCT for children or adults with SCD using a variety of graft sources as well as conditioning and GVHD ...

8. ashpublications.org ashpublications.org/blood/article/143/25/2654/515325/An-international-learning-collaborative-phase-2

An international learning collaborative phase 2 trial for ... For most adults with sickle cell disease, haploidentical BMT with thiotepa + PTCy is now a widely available curative option with excellent ...

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

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... The meta-analysis of 58 studies (n = 7931) revealed allo-HSCT to have 94%, 86%, 20%, 14%, 9%, and 6% for overall survival (OS), event-free ...