Non-Myeloablative Bone Marrow Transplant for Sickle Cell Disease

Not currently recruiting at 2 trial locations

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt-Ingram Cancer Center

Disqualifiers: Poor cardiac, pulmonary, liver function, HIV, others

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

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 new bone marrow transplant approach for people with sickle cell disease, focusing on minimizing side effects and improving outcomes. The researchers are testing a non-myeloablative method, which uses less intense pre-treatment to make the transplant safer and more accessible. This method is particularly suited for those unable to undergo a traditional transplant due to donor issues or severe side effects. Individuals with sickle cell disease who experience severe symptoms, such as frequent pain despite treatment or chronic lung or kidney problems, might be suitable candidates for this trial.

As an unphased trial, this study provides a unique opportunity for patients to access innovative treatment options that may not be available elsewhere.

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

The trial information does not specify if you need to stop your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this non-myeloablative bone marrow transplant is safe for sickle cell disease?

Research has shown that a less intense type of stem cell transplant, called non-myeloablative bone marrow transplantation, is generally safe for people with sickle cell disease. In one study, 94% of patients remained alive, and 86% did not experience severe complications from the transplant. Importantly, the risk of dying from this treatment was low, at 6%.

Patients have experienced fewer problems with graft-versus-host disease, a condition where donor cells attack the recipient's body. Graft failure, where the transplanted cells do not function properly, occurred in about 5.4% of patients, and graft rejection, where the body rejects the new cells, occurred in 7.5% of cases.

Overall, these findings suggest that the treatment is well-tolerated and safe for those unable to undergo more intense transplants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for sickle cell disease, which mainly focus on managing symptoms and preventing complications, the non-myeloablative bone marrow transplant approach aims to address the root cause by replacing the patient’s defective bone marrow with healthy donor marrow. Researchers are excited because this method is less intense than traditional bone marrow transplants, making it safer and more accessible for patients who may not tolerate full-intensity conditioning. Additionally, the use of immunosuppressive drugs like Cyclophosphamide, Fludarabine, Mycophenolate mofetil, and Sirolimus in combination with reduced-intensity conditioning could potentially establish a stable and healthy blood system with fewer side effects. This approach offers hope for a more permanent solution to sickle cell disease, shifting the focus from symptom management to long-term disease modification.

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

Research has shown that a less intense type of bone marrow transplant, known as non-myeloablative transplantation, can effectively treat sickle cell disease. This trial will evaluate the effectiveness of this approach. Studies indicate that when performed at a young age, this transplant allows over 90% of patients to live without the disease. This method avoids the need for strong chemotherapy or radiation, typically required in traditional transplants, and enables the donor's bone marrow to successfully engraft with fewer side effects. Early results suggest that this approach can lead to long-term remission of the disease. Overall, non-myeloablative transplants offer a promising option for those unable to undergo more intense treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Adetola A Kassim, MD

Principal Investigator

Vanderbilt-Ingram Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with sickle cell anemia or related hemoglobin disorders, aged 1-70 years, who have a compatible first-degree relative donor willing to donate bone marrow. Participants must not be pregnant, HIV-positive, or have severe organ dysfunction. They should be able to consent and commit to all treatment stages.

Inclusion Criteria

Patients must be geographically accessible and willing to participate in all stages of treatment.

Patients and donors must be able to sign consent forms. First degree relative should be willing to donate

I am fully active or able to carry out light work.

Exclusion Criteria

Pulmonary hypertension moderate to severe by echocardiographic standards.

HIV-positive

My lung function tests are very low.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Non-Myeloablative Conditioning

Participants undergo a non-myeloablative conditioning regimen to prepare for bone marrow transplantation

2-3 weeks

Bone Marrow Transplantation

Participants receive allogeneic bone marrow transplantation

1 day

Follow-up

Participants are monitored for safety, effectiveness, and transplant-related outcomes

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bone marrow transplantation
• Cyclophosphamide (CTX)
• Fludarabine
• Mesna
• Mycophenolate mofetil (MMF)
• Sirolimus
• Thymoglobulin
• Total body irradiation

Trial Overview The study tests a non-myeloablative conditioning regimen before bone marrow transplantation (alloBMT) in patients with sickle cell disease and thalassemia. It aims to reduce toxicity by using immunosuppressive drugs like Thymoglobulin and Sirolimus instead of high-dose chemotherapy or radiation.

How Is the Trial Designed?

Group I: Non-Myeloablative Conditioning and Bone Marrow Transplantation Experimental Treatment 8 Interventions

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11960486/

Clinical Outcomes Among Patients With Sickle Cell ... The purpose of this study is to synthesize evidence on disease-specific outcomes in patients with sickle cell disease (SCD) or transfusion-dependent beta- ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1319016424000999

The effectiveness of hematopoietic stem cell ... Patients with sickle cell disease have been demonstrated to have a disease-free survival rate of more than 90 % when a transplant is performed on a young ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4698790/

Nonmyeloablative HLA-Matched Sibling Allogeneic ... Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell disease, but toxicity may be ...

4. ashpublications.org ashpublications.org/bloodadvances/article/9/4/877/526317/Is-allogeneic-transplantation-for-sickle-cell

Is allogeneic transplantation for sickle cell disease still ... Both genetic therapy and allo-HCT offer the potential for cure for most with SCD. However, the cost (∼5 times higher), the current need for myeloablation, and ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ajh.27295

Favorable outcome of non‐myeloablative allogeneic ... Herein, we are reporting our long-term outcome data of non-myeloablative (NMA) HSCT in adults with severe SCD with emphasis on factors ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725014472

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... Allo-HSCT in SCD has OS, EFS, and mortality rates of 94%, 86% and 6%, respectively. •. NMA conditioning has the lowest aGVHD, cGVHD, and ...

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

An international learning collaborative phase 2 trial for ... The event-free survival probabilities at 2 years for children and adults were 68.4% (95% CI: 49.1-81.6) and 94.7% (95% CI: 80.6-98.7), ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4581443/

Blood and marrow transplantation for sickle cell disease Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97%, respectively. Nine patients had graft failure ...