Stem Cell Transplant for Sickle Cell Disease

(HaploSCD Trial)

Recruiting at 5 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: New York Medical College

Disqualifiers: Pregnancy, Uncontrolled infection, Fibrosis, 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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to determine the safety and outcome (long-term control) of a high-dose chemotherapy regimen followed by an infusion of CD34 selected (immune cells) stem cells from a partially matched adult family member donor, called haploidentical stem cell transplantation, in high-risk sickle cell disease patients. Funding Source - FDA OOPD

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.

What data supports the effectiveness of the treatment CD34 selected T-cell depleted allogeneic SCT for sickle cell disease?

Research shows that allogeneic stem cell transplantation (a treatment using donor stem cells) is currently the only curative option for sickle cell disease, with high survival rates and the ability to cure many patients. Additionally, CD34+ cell selection helps reduce complications like graft-versus-host disease, making it a promising approach for treating sickle cell disease. ^{1 2 3 4 5}

Is CD34+ selected T-cell depleted stem cell transplant safe for humans?

CD34+ selected T-cell depleted stem cell transplants have been shown to reduce the risk of graft-versus-host disease (GVHD), a common complication, and have been used successfully in patients with conditions like leukemia and sickle cell disease. However, there are risks such as infection, organ toxicity, and posttransplant lymphoproliferative disorder (PTLD), which occurred in some patients. Overall, studies show promising safety outcomes with low incidence of severe complications. ^{2 6 7 8 9}

How is the CD34 selected T-cell depleted allogeneic SCT treatment different for sickle cell disease?

This treatment is unique because it involves a special process to remove certain immune cells (T-cells) from the donor stem cells, which helps reduce the risk of graft-versus-host disease (a condition where the donor cells attack the patient's body) while still providing a curative option for sickle cell disease. ^{1 2 3 4 10}

Research Team

Mitchell S Cairo, MD

Principal Investigator

New York Medical College

Eligibility Criteria

This trial is for high-risk sickle cell disease patients who've had multiple painful events, adequate organ function, and specific complications like stroke or acute chest syndrome. They need a partially matched family donor and can't be pregnant, breastfeeding, non-compliant with medical care, have significant liver fibrosis/cirrhosis or previous stem cell transplants.

Inclusion Criteria

I have had a stroke or brain injury related to my sickle cell disease.

I have had at least 3 painful episodes in the last 2 years.

My kidney, liver, heart, and lungs are working well.

Exclusion Criteria

Demonstrated lack of compliance with medical care.

I have severe liver scarring.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive a high-dose chemotherapy regimen as part of the conditioning process

4-6 weeks

Stem Cell Transplantation

Infusion of CD34 selected T-cell depleted allogeneic stem cells from a haploidentical donor

1 week

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes such as donor chimerism and organ function

4 years

Treatment Details

Interventions

• CD34 selected T-cell depleted allogeneic SCT

Trial Overview The study tests the safety and effectiveness of high-dose chemotherapy followed by an infusion of immune cells from a family member to manage sickle cell disease. It aims to see if this approach offers long-term control over the condition.

Participant Groups

Group I: Haplo Stem Cell Transplantation Experimental Treatment 1 Intervention

CD34 selected T-cell depleted allogeneic SCT

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials

73

Recruited

8,700+

Miltenyi Biomedicine GmbH

Industry Sponsor

Trials

38

Recruited

1,700+

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborator

Trials

275

Recruited

5,182,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

UCSF Benioff Children's Hospital Oakland

Collaborator

Trials

80

Recruited

19,100+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Tufts Medical Center

Collaborator

Trials

264

Recruited

264,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Findings from Research

In a study of 29 sickle cell disease patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), T-cell neogenesis was initially normal but declined post-transplant, fully restoring to healthy levels by one year, while B-cell neogenesis remained elevated throughout follow-up.

The presence of increased IL-10-producing B-regulatory cells after transplantation suggests a potential improvement in immune regulation and homeostasis, which may be beneficial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation resets T- and B-cell compartments in sickle cell disease patients. Jarduli-Maciel, LR., de Azevedo, JTC., Clave, E., et al.[2022]

A study of 506 adult patients receiving CD34+ selected hematopoietic stem cell transplants showed that using a combined prognostic model of Disease Risk Index (DRI) and Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) can effectively predict overall survival and relapse-free survival outcomes.

Patients with a high DRI had a significantly increased risk of death and relapse compared to those with low/intermediate DRI, indicating that this model can help in selecting the best candidates for CD34+ selected transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining the Disease Risk Index and Hematopoietic Cell Transplant Co-Morbidity Index provides a comprehensive prognostic model for CD34+-selected allogeneic transplantation. Cho, C., Hilden, P., Avecilla, ST., et al.[2022]

Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shown to be curative for children with sickle cell disease (SCD), but recent advancements in nonmyeloablative allo-HSCT have made it a viable option for adults, leading to stable mixed hematopoietic chimerism and normalization of blood counts.

The potential for immunologic tolerance in adults receiving nonmyeloablative allo-HSCT suggests that this approach could safely expand treatment options for SCD patients, including the use of alternative donor sources, thereby increasing the accessibility of curative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for sickle cell disease: the time is now. Hsieh, MM., Fitzhugh, CD., Tisdale, JF.[2021]

In a study of 20 adult patients with sickle cell disease who underwent stem cell transplantation, a conditioning regimen combining fludarabine, busulfan, anti-T-cell lymphocyte globulin, and low-dose total body irradiation resulted in successful donor cell engraftment without any cases of graft rejection or severe graft-versus-host disease (GVHD).

The treatment showed promising outcomes with no non-relapse mortality and a low incidence of major complications, suggesting that this transplantation approach could be a safe and effective option for adults with sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogenic peripheral stem cell transplantation from HLA-matched related donors for adult sickle cell disease: remarkable outcomes from a single-center trial. Ozdogu, H., Boga, C., Yeral, M., et al.[2019]

In a study of 36 patients with sickle cell disease undergoing nonmyeloablative HLA-matched stem cell transplantation, 28% had pre-existing HLA class I antibodies, which led to increased platelet transfusion requirements post-transplant.

Patients with RBC alloantibodies required more red blood cell transfusions and showed significantly lower donor T cell chimerism at one year, indicating that pre-existing RBC alloimmunization may negatively impact long-term engraftment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of pre-existing HLA and red blood cell antibodies on transfusion support and engraftment in sickle cell disease after nonmyeloablative hematopoietic stem cell transplantation from HLA-matched sibling donors: A prospective, single-center, observational study. Nickel, RS., Flegel, WA., Adams, SD., et al.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation resets T- and B-cell compartments in sickle cell disease patients. [2022]

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

Combining the Disease Risk Index and Hematopoietic Cell Transplant Co-Morbidity Index provides a comprehensive prognostic model for CD34+-selected allogeneic transplantation. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell transplantation for sickle cell disease: state of the science. [2022]

4. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Alternative donor: αß/CD19 T-cell-depleted haploidentical hematopoietic stem cell transplantation for sickle cell disease. [2020]

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

Allogeneic hematopoietic stem cell transplantation for sickle cell disease: the time is now. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Allogeneic Stem Cell Transplantation with CD34+ Cell Selection. [2021]

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

Alternative donor hematopoietic stem cell transplantation for sickle cell disease. [2022]

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

Hematopoietic stem cell transplantation for sickle cell disease: current practice and emerging trends. [2016]

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

Allogenic peripheral stem cell transplantation from HLA-matched related donors for adult sickle cell disease: remarkable outcomes from a single-center trial. [2019]

10. England pubmed.ncbi.nlm.nih.gov

The impact of pre-existing HLA and red blood cell antibodies on transfusion support and engraftment in sickle cell disease after nonmyeloablative hematopoietic stem cell transplantation from HLA-matched sibling donors: A prospective, single-center, observational study. [2022]