Stem Cell Transplant for Sickle Cell Anemia

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

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

Must be taking: Immunosuppressants

Disqualifiers: Pregnancy, Infections, Organ failure, others

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

Compensation: Varies

Number of Visits: 3

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new bone marrow transplant method for adults with sickle cell disease and Beta-thalassemia. It uses stem cells from a half-matched family donor, low-dose radiation, and immunosuppressant drugs, but no chemotherapy. The goal is to reduce complications and improve outcomes for patients who lack fully matched donors.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, since the trial involves immunosuppressant therapy and other treatments, it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment for sickle cell anemia?

Research shows that peripheral blood stem cell transplantation (PBSC) is effective in treating advanced blood cancers and severe aplastic anemia, with benefits like faster recovery and improved survival rates. This suggests potential effectiveness for sickle cell anemia, although specific data for this condition is not provided. ^{1 2 3 4 5}

Is peripheral blood stem cell (PBSC) transplantation generally safe for donors?

PBSC transplantation is generally safe for donors, with a lower risk of serious adverse events compared to bone marrow donation. Some side effects like muscle and bone pain, and rare serious complications like spleen enlargement, can occur but are usually manageable. ^{5 6 7 8 9}

How is the PBSC transplant treatment different from other treatments for sickle cell anemia?

The PBSC transplant treatment for sickle cell anemia is unique because it uses stem cells from the blood instead of the bone marrow, which can be less invasive and may offer a new solution for patients who are highly sensitized and have difficulty finding a donor. This approach also uses a nonradiation-based conditioning regimen, which can be less toxic and help in successful engraftment of donor cells. ^{7 10 11 12 13}

Research Team

Courtney D Fitzhugh, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

Adults diagnosed with severe congenital anemias like sickle cell disease or Beta-thalassemia, who have a half-matched family donor. Candidates should be at high risk due to organ damage or complications not improved by other treatments. They must understand and consent to the trial, not be pregnant, and meet specific health criteria.

Inclusion Criteria

My condition is specific to the disease being studied.

I have sickle cell disease with severe complications not improved by hydroxyurea.

Non-disease specific:

Exclusion Criteria

Pregnant or lactating

Major ABO mismatch

I need help with my daily activities due to my health condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Conditioning

Recipients receive low-dose radiation and immunosuppressant therapy with alemtuzumab and sirolimus before the transplant.

2 days

2 visits (in-person)

Transplantation

Recipients receive donor stem cells through a central line, followed by blood transfusions and antibiotics as necessary.

1 day

1 visit (in-person)

Post-Transplant Monitoring

Physical and laboratory examinations occur weekly or twice weekly to monitor engraftment and manage complications.

100 days

Weekly or twice weekly visits (in-person)

Follow-up

Participants are monitored every 6 months for 5 years to assess long-term outcomes such as GVHD and survival.

5 years

Biannual visits (in-person)

Treatment Details

Interventions

• Alemtuzumab
• Cyclophosphamide
• Low Dose Irradiation
• PBSC Transplant
• Sirolimus

Trial Overview The trial is testing a bone marrow transplant (BMT) using stem cells from half-matched donors combined with low-intensity radiation and immunosuppressant drugs (Alemtuzumab, Sirolimus, Cyclophosphamide). It aims to cure anemia without full chemotherapy's side effects.

Participant Groups

Group I: Cohort 3 Experimental Treatment 5 Interventions

PBSC transplant with 100 mg/kg post-transplant cyclophosphamide (PT-Cy)

Group II: Cohort 2 Experimental Treatment 5 Interventions

PBSC transplant with 50 mg/kg post-transplant cyclophosphamide (PT-Cy)

Group III: Cohort 1 Experimental Treatment 4 Interventions

PBSC transplant with no post-transplant cyclophosphamide (PT-Cy)

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Findings from Research

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]

The use of peripheral blood stem cells (PBSC) for allogeneic transplantation has significantly increased over the past 9 years, with over 50% of sibling and 25% of unrelated donor transplants utilizing PBSC, primarily due to faster recovery of blood cell production.

Randomized trials indicate that PBSC transplantation offers a survival advantage for patients with advanced leukemia, mainly by reducing transplant-related mortality, although it is associated with a higher risk of chronic graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation using peripheral blood stem cells. Russell, NH., Byrne, JL.[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]

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]

Peripheral blood stem cells (PBSC) are increasingly used for hematopoietic stem cell transplants, with mobilization strategies like chemotherapy and growth factors significantly increasing the yield of CD34+ cells, which are crucial for transplantation.

While PBSC collection is generally effective, it can lead to side effects such as citrate reactions, thrombocytopenia, and in rare cases, serious complications like spleen rupture, particularly in allogeneic donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mobilization and harvesting of peripheral blood stem cells. Moog, R.[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]

References

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

Allogeneic peripheral blood stem cell transplantation: clinical overview and nursing implications. [2005]

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

Guiding patients and their families through peripheral stem cell transplantation with the help of a teaching booklet. [2007]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation using peripheral blood stem cells. [2005]

4. China pubmed.ncbi.nlm.nih.gov

Allogeneic peripheral blood stem cell transplantation in the treatment of severe aplastic anemia and severe infection. [2004]

5. Japan pubmed.ncbi.nlm.nih.gov

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

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Mobilization and harvesting of peripheral blood stem cells. [2019]

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

Effective collection of peripheral blood stem cells in children weighing 20 kilogram or less in a single large-volume apheresis procedure. [2019]

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

Lower risk for serious adverse events and no increased risk for cancer after PBSC vs BM donation. [2022]

9. England pubmed.ncbi.nlm.nih.gov

PBSC collection from family donors in Japan: a prospective survey. [2021]

10. Italy pubmed.ncbi.nlm.nih.gov

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

11. Italy pubmed.ncbi.nlm.nih.gov

Clinical use of allogeneic hematopoietic stem cells from sources other than bone marrow. [2005]

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

Stem cell transplantation eliminates alloantibody in a highly sensitized patient. [2019]

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

Higher mortality after allogeneic peripheral-blood transplantation compared with bone marrow in children and adolescents: the Histocompatibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry. [2007]