Stem Cell Transplant for Sickle Cell Disease

Overseen By Lisa Pullens, RN

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Prior transplants, Active infection, Malignancy, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating severe sickle cell disease using a blood stem cell transplant. The focus is on using half-matched donors, such as a parent or sibling, to generate healthy blood cells and reduce complications. Researchers are also exploring a new combination of medicines, including CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant, to prepare patients for the transplant, aiming to enhance recovery and quality of life. Individuals with sickle cell disease who experience frequent pain crises or other severe symptoms and lack a fully matched donor might be suitable for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use certain investigational agents, chemotherapy, biological therapy, or radiation therapy, and you cannot use moderate and strong CYP3A4 inhibitors. It's best to discuss your current medications with the trial team.

What prior data suggests that this stem cell transplant is safe for sickle cell disease patients?

Research shows that blood stem cell transplants, like the one being tested, have been safely used in patients with sickle cell disease. One study demonstrated that adults with severe sickle cell disease were successfully treated with a transplant from partially matched donors, proving this method can be effective. Importantly, the transplant process involves removing certain immune cells to improve results and reduce complications.

The treatment is generally well-tolerated, especially when using a gentler form of chemotherapy that doesn't completely destroy the bone marrow. This approach can help reduce side effects and speed up recovery. Data from similar treatments show high survival rates, indicating that patients usually handle these transplants well.

These studies provide promising safety evidence, but this specific version of the treatment is being tested for the first time. While past results are encouraging, this research will help confirm its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for sickle cell disease, which often include blood transfusions and hydroxyurea, the CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant offers a novel approach by using stem cells. This treatment is unique because it involves a minimally manipulated transplant product specifically designed to reduce immune rejection. Researchers are excited about this method as it uses a specialized conditioning regimen that may allow for successful transplantation with fewer side effects and improved patient outcomes.

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

Research shows that a specific type of stem cell transplant, known as a CD4+ T-cell-depleted haploidentical hematopoietic transplant, can effectively treat sickle cell disease (SCD). Participants in this trial will receive the transplant following a nonmyeloablative conditioning regimen. Studies have found that this transplant is currently the only cure for individuals with SCD symptoms. It can enhance patients' quality of life by enabling the production of normal red blood cells. Recent advancements have led to high survival rates; one study reported a 100% overall survival rate and a 92% disease-free survival rate for similar treatments. This method offers hope for reversing sickle cell disease and reducing its complications. ^{2 4 5 6 7}

Who Is on the Research Team?

Joseph Rosenthal, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with severe sickle cell disease who have had multiple joint issues, strokes, or vaso-occlusive crises despite treatment. They need a related half-matched donor (like a parent or sibling) and can't have had prior transplants. Women must not be pregnant and agree to use contraception.

Inclusion Criteria

I have had a stroke or neurological issues lasting more than a day.

I have been diagnosed with sickle cell disease (SS or S-βº Thalassemia).

I don't have a fully matched donor for a transplant.

Exclusion Criteria

I have serious liver scarring and have been on blood transfusion therapy for over 6 months.

I am not pregnant or breastfeeding.

I have had a bone marrow transplant in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Non-myeloablative Conditioning

Participants receive a 21-day non-myeloablative conditioning regimen with cyclophosphamide, pentostatin, and rabbit anti-thymocyte globulin

3 weeks

Multiple visits for drug administration

Transplantation

Participants receive a CD4+ T-cell-depleted haploidentical hematopoietic cell transplant

1 day

1 visit (in-patient)

Immunosuppressant Therapy

Participants receive immunosuppressants (tacrolimus and mycophenolate mofetil) starting from Day -1 post-transplant

Until discontinuation post-transplant

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of donor chimerism

Up to 2 years post-transplant

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant
• Cyclophosphamide
• Mycophenolate mofetil
• Pentostatin
• Rabbit anti-thymocyte globulin
• Tacrolimus

Trial Overview The study tests a blood stem cell transplant from a half-matched relative using new chemotherapy that's less harsh on bone marrow. It aims to create mixed chimerism where the patient's body accepts both their own and the donor's blood cells, potentially reversing sickle cell disease.

How Is the Trial Designed?

Group I: COH-MC-17 and immunosuppressants Experimental Treatment 6 Interventions

Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0. Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant. The minimally manipulated transplant product is manufactured using the CliniMACS device.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Published Research Related to This Trial

Haploidentical stem cell transplantation (haploHCT) offers a life-saving option for high-risk sickle cell disease patients without matched donors, but it faces challenges like graft failure and graft-versus-host disease (GvHD).

Recent strategies, including T-cell depletion methods and post-transplant cyclophosphamide, aim to improve engraftment rates while minimizing GvHD, and achieving stable mixed chimerism post-transplant has shown promise for better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical stem cell transplantation for patients with sickle cell disease: current status. Pawlowska, AB., Sun, V., Rosenthal, J.[2022]

In a study of 50 adult patients with sickle cell disease referred for haploidentical hematopoietic stem cell transplantation (HSCT), only 10 patients underwent the procedure, highlighting challenges such as insurance denial and patient reluctance.

The modified Hopkins regimen used for HSCT resulted in a high engraftment rate of 87.5% and low morbidity, with 87.5% of patients alive at a median follow-up of 16 months, suggesting its potential for broader application in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease. Saraf, SL., Oh, AL., Patel, PR., et al.[2023]

A nonmyeloablative bone marrow transplantation approach using related and HLA-haploidentical donors has been developed for sickle cell disease, showing a low risk of complications and allowing for a broader donor pool.

In a study of 17 patients, 11 achieved durable engraftment, with 10 patients remaining asymptomatic and only one case of mild acute graft-versus-host disease, indicating the treatment's safety and potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Bolaños-Meade, J., Fuchs, EJ., Luznik, L., et al.[2022]

Haploidentical hematopoietic stem-cell transplantation offers a viable option for patients lacking HLA-matched donors, with recent advancements reducing issues like graft failure and graft-versus-host disease (GVHD) through improved T cell depletion methods.

Despite these improvements, challenges such as prolonged immune deficiency and increased relapse rates persist, but new strategies like partial T cell depletion and posttransplant therapies show promise for enhancing immune recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical hematopoietic stem-cell transplantation in adults. Alshemmari, S., Ameen, R., Gaziev, J.[2021]

Related haploidentical hematopoietic stem cell transplant (HCT) offers a promising alternative for treating sickle cell disease (SCD), expanding the donor pool to about 90% of eligible patients, including adults with significant health issues.

Three emerging haploidentical HCT strategies show potential for curative therapy in SCD, with nonmyeloablative approaches allowing for better tolerance in adults and reducing treatment-related deaths compared to traditional myeloablative methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The range of haploidentical transplant protocols in sickle cell disease: all haplos are not created equally. Kassim, AA., DeBaun, MR.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10567813/

Excellent outcome of stem cell transplantation for sickle ... Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative option for symptomatic SCD and can improve quality of ...

2. nature.com nature.com/articles/s41409-025-02546-w

αß T-cell depleted haploidentical stem cell transplantation ... At a median follow-up of 37 months (range 6–90), overall survival (OS) was 100% with a disease-free survival (DFS) of 100% in MSD and 92% in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725014472?via%3Dihub

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... Recent advancements have improved the overall outcomes of allo-HSCT in SCD. ABSTRACT. Sickle cell disease (SCD) is a life-threatening hemolytic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10947844/

Long-term outcomes after unrelated donor transplantation for ... The trial met a pre-specified primary endpoint of 75% 1-year event-free survival (EFS). However, as previously reported, the incidence of 1-year acute and ...

5. astctjournal.org astctjournal.org/article/S2666-6367(25)01272-2/fulltext

Outcomes of Unrelated Donor Stem Cell Transplantation ... Median follow-up is 36 months (range 10 to 57). One- and 3-year overall survival is 93.8%, and 3-year graft failure-free survival is 81.3%. One patient with ...

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

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... In this systematic review and meta-analysis, we assessed the safety and efficacy of allo-HSCT in SCD, offering information on results for ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4915/503568/Haploidentical-A-T-Cell-Depleted-HSCT-Represents

Haploidentical Aß T Cell Depleted HSCT Represents an ... Results: The OS and DFS for MSD and T-haplo-HSCT was 95% and 83%, respectively (Table 1). The median follow-up was 49 months for MSD (range 5- ...