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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for treating sickle cell disease and Beta-thalassemia using stem cell transplants. Researchers aim to determine if a half-matched donor with less intense treatment—avoiding heavy chemotherapy and using low-dose radiation and immunosuppressant drugs—can be effective and safe. The trial compares different doses of the immunosuppressant drug cyclophosphamide to assess how well they prevent donor cell rejection. Suitable participants are those over 18 with sickle cell disease or Beta-thalassemia who have a family member as a half-match for stem cell donation. As a Phase 1/Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Peripheral Blood Stem Cell (PBSC) transplants for sickle cell disease are generally safe. Studies indicate that using half-matched donors is well-tolerated and leads to good outcomes. For instance, a review found a high survival rate of 94% in patients with sickle cell disease who received these transplants.

Early findings suggest that collecting these stem cells is safe and well-tolerated by donors. Additionally, the preparation for the transplant did not cause severe side effects in patients.

Regarding cyclophosphamide, a drug used to suppress the immune system after the transplant, research shows it is safe. It helps lower the risk of graft-versus-host disease, where donor cells attack the recipient's body. This method has proven effective and safe.

Overall, past studies have found these treatments to be generally safe, with manageable side effects and promising results.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for sickle cell anemia because they explore the potential of PBSC (Peripheral Blood Stem Cell) transplants, which could offer a more direct way to address the root cause of the disease. Unlike conventional treatments like hydroxyurea or blood transfusions, which primarily focus on managing symptoms, PBSC transplants aim to replace the faulty blood-forming stem cells with healthy ones. This trial examines different approaches to post-transplant care, including varying doses of cyclophosphamide, which could help reduce the risk of complications and improve success rates. By potentially offering a more effective and long-term solution, these treatments could significantly improve the quality of life for people with sickle cell anemia.

What evidence suggests that this trial's treatments could be effective for sickle cell anemia?

Research has shown that stem cell transplants can effectively treat sickle cell disease. In one study, 94% of patients survived after receiving this type of transplant. Another study found that using partially matched donors with a special preparation worked as well as using fully matched donors.

In this trial, participants will receive a PBSC transplant, with some cohorts receiving different dosages of post-transplant cyclophosphamide (PT-Cy). Cyclophosphamide, a drug that prevents the body from rejecting the transplant, has improved results. It helps the transplant take hold and reduces the risk of graft-versus-host disease, where donor cells attack the recipient's body. This suggests that combining stem cell transplants with cyclophosphamide may effectively treat sickle cell disease.12356

Who Is on the Research Team?

CD

Courtney D Fitzhugh, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

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:
See 32 more

Exclusion Criteria

Pregnant or lactating
Major ABO mismatch
I need help with my daily activities due to my health condition.
See 4 more

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: Cohort 3Experimental Treatment5 Interventions
Group II: Cohort 2Experimental Treatment5 Interventions
Group III: Cohort 1Experimental Treatment4 Interventions

Find a Clinic Near You

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

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.
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]
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.
Mobilization and harvesting of peripheral blood stem cells.Moog, R.[2019]
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.
[Peripheral blood stem cell transplantation: present status and future prospects].Takaue, Y.[2006]

Citations

Hematopoietic stem-cell transplantation for sickle cell diseaseThough human leukocyte antigen (HLA) matched sibling donor (MSD) transplants offer the best outcomes for SCD, less than 14% of patients with SCD have such ...
Assessment of Safety and Efficacy of Peripheral Blood ...We previously demonstrated 100% EFS/overall survival in 18 children with SCD following reduced toxicity conditioning and HLA matched sibling or cord blood (CB) ...
Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ...This systematic review and meta-analysis present strong evidence for the safety and efficacy of allo-HSCT in SCD treatment, with an OS of 94% ...
Stem Cell Transplantation in Advanced Stage Sickle Cell ...Stem Cell Transplantation in Advanced Stage Sickle Cell Disease with Haploidentical T-Cell Depleted PBSC Yields Comparable Outcomes to Matched ...
Stem cell transplantation in sickle cell disease - PubMed CentralData from the BM arm of the SCURT trial was recently published, showing an EFS and OS of 69% and 79% respectively, and a TRM of 28% of which there were 7 GVHD ...
Haploidentical Peripheral Blood Stem Cell Transplantation ...Allogeneic nonmyeloablative hematopoietic stem cell transplantation (HSCT) from HLA-matched related donors results in event-free survival rates of 87% to 92%, ...
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