Bone Marrow Transplant for Sickle Cell Disease

Not currently recruiting at 25 trial locations

Overseen By Study Information

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Disqualifiers: Liver fibrosis, Lung disease, Renal dysfunction, Cardiac dysfunction, Neurologic impairment, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a bone marrow transplant treatment for children with sickle cell disease (SCD). The aim is to reduce the intensity of transplant preparation, enhancing safety and effectiveness. Specific medications, including Alemtuzumab (also known as Campath, Lemtrada, or MabCampath), Fludarabine, and Melphalan, prepare the body to accept healthy donor cells. Ideal candidates are children under 13 with SCD who have a sibling donor without the disease and experience serious symptoms like frequent pain episodes or past strokes. Researchers will closely monitor participants for two years after the transplant to track improvements and any side effects. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

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

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves chemotherapy and other medicines for conditioning, it's possible that some medications might need to be adjusted. It's best to discuss this with the trial team.

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

Research shows that combining alemtuzumab, fludarabine, and melphalan in bone marrow transplants is promising for safety. Studies indicate that many patients tolerate this treatment well.

In one study, this treatment produced good results with fewer severe side effects for many patients. Another study involving children with sickle cell disease found that this approach caused fewer harmful side effects.

However, some risks exist, such as graft-versus-host disease (GVHD), where the new cells might attack the body. Despite these risks, the overall findings suggest that these treatments are relatively safe when closely monitored.

For those considering joining a trial, these results might reassure about the treatment's safety. Always consult healthcare professionals to understand what these findings mean for specific situations. ^{1 2 3 4 5}

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

Unlike the standard treatments for sickle cell disease, which often focus on managing pain and preventing complications, the combination of alemtuzumab, fludarabine, and melphalan (FAM) used in this trial offers a reduced intensity conditioning regimen for bone marrow transplants. This approach is exciting because it aims to make transplants safer and more accessible for children with sickle cell disease by minimizing the harsh side effects typically seen with traditional, high-intensity conditioning regimens. Researchers are hopeful that using FAM with a matched sibling donor could potentially cure sickle cell disease by replacing the defective bone marrow with healthy cells, offering a long-term solution rather than just symptom management.

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

This trial will evaluate the use of a combination of alemtuzumab, fludarabine, and melphalan in bone marrow transplants for patients with sickle cell disease. This combination, known as reduced intensity conditioning (RIC), helps the body accept donor cells by using lower doses of chemotherapy. Studies have shown that this method can lead to fewer side effects and successful outcomes, such as improved blood health. Previous experiences with RIC demonstrated good results and lower risks of complications, such as mixed chimerism, where both donor and recipient cells coexist. These findings suggest that this treatment may effectively help young sickle cell patients receive successful transplants. ^{1 4 6 7 8}

Who Is on the Research Team?

Ann Haight, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for pre-adolescent children under 13 with sickle cell disease who've had multiple episodes of acute chest syndrome or vaso-occlusive pain, and have a healthy sibling donor also under 13. Candidates must not have severe neurological impairments, organ dysfunction, HIV infection, or uncontrolled infections.

Inclusion Criteria

I have a brain condition without symptoms, confirmed by specific brain scans.

I have had a stroke with symptoms lasting over 24 hours and confirmed by brain scans.

- Co-enrollment on STAR Project Sickle Cure (PSC) study is required for sites that are activated and participating in the study

Exclusion Criteria

My parent or guardian does not understand the risks of the HSCT process.

I cannot undergo a bone marrow harvest or general anesthesia due to health or personal reasons.

- Donor is HIV infected

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-3 months

Conditioning

Participants undergo conditioning with chemotherapy and other medicines to prepare for the transplant

3 weeks

Inpatient stay

Transplantation

Participants receive the bone marrow transplant

1 day

Inpatient stay

Post-Transplant Hospitalization

Participants remain in the hospital for recovery and monitoring after the transplant

4-6 weeks

Inpatient stay

Outpatient Follow-up

Participants are followed closely in the clinic with frequent visits for 6 to 12 months

6-12 months

Frequent clinic visits

Long-term Follow-up

Routine medical care and yearly examinations for many years after transplant

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Alemtuzumab
• Fludarabine
• Melphalan

Trial Overview The study tests the effectiveness of a bone marrow transplant from an HLA-matched sibling in treating sickle cell disease. Participants will undergo chemotherapy (Fludarabine, Alemtuzumab, Melphalan) to prepare their body for the transplant.

How Is the Trial Designed?

Group I: Reduced Intensity Conditioning with FAM Experimental Treatment 3 Interventions

Children with SCD will received reduced intensity conditioning with fludarabine, alemtuzumab and melphalan (FAM) during HSCT with a HLA matched sibling donor

Alemtuzumab is already approved in United States, European Union for the following indications:

Approved in United States as Campath for:

• Chronic lymphocytic leukemia
• Multiple sclerosis

Approved in European Union as Lemtrada for:

• Multiple sclerosis

Approved in European Union as Campath for:

• Chronic lymphocytic leukemia

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4603747/

Experience with Alemtuzumab, Fludarabine, and ... We conclude that alemtuzumab, fludarabine, and melphalan RIC HCT offers good results for many patients and that the risk of developing mixed chimerism is ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0966327425000073

Comparison of outcomes following subcutaneous or ... To compare adverse effects and efficacy outcomes between intravenous and subcutaneous alemtuzumab administration in pediatric patients with sickle cell disease ...

3. astctjournal.org astctjournal.org/article/S1083-8791(16)30288-9/fulltext

A Single-Center Experience Comparing Alemtuzumab, ... To estimate the success of alemtuzumab, fludarabine, and melphalan RIC HSCT for patients with CGD, we report the outcomes of 4 patients who received alemtuzumab ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02766465?cond=%22Sickle%20Cell%20Disease%22&intr=%22fludarabine%20phosphate%22&viewType=Table&rank=10&tab=results

Study Results | Bone Marrow Transplantation vs Standard ... Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study. Am J Hematol. 2019 ...

5. ashpublications.org ashpublications.org/blood/article/127/4/503/35046/Alemtuzumab-levels-impact-acute-GVHD-mixed

Alemtuzumab levels impact acute GVHD, mixed chimerism ... Experience with alemtuzumab, fludarabine, and melphalan reduced intensity conditioning hematopoietic cell transplantation in patients with nonmalignant ...

6. astctjournal.org astctjournal.org/article/S2666-6367(25)00300-8/fulltext

Alemtuzumab, Fludarabine, Melphalan, and Thiotepa As a ... We report results of a phase 2 trial using a reduced intensity conditioning (RIC) regimen consisting of alemtuzumab, fludarabine, melphalan, and thiotepa for ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S003719631730032X

Allogeneic hematopoietic cell transplantation from matched ... Baker, et al. Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease.

8. ashpublications.org ashpublications.org/blood/article/128/21/2561/35735/A-trial-of-unrelated-donor-marrow-transplantation

A trial of unrelated donor marrow transplantation for children ... Children with sickle cell disease engrafted unrelated donor marrow after reduced intensity conditioning. A high incidence of GVHD and ...