Stem Cell Transplant for Sickle Cell Disease

Overseen By Lani Krauz, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Illinois at Chicago

Must be taking: Immune-suppressive agents

Disqualifiers: HIV, Pregnancy, Cirrhosis, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new stem cell transplant method for individuals with severe sickle cell disease, particularly those unable to take or who have had issues with hydroxyurea, a common treatment. The goal is to determine if special immune-suppressing drugs, such as Alemtuzumab (also known as Campath, Lemtrada, or MabCampath) and Sirolimus (also known as Rapamune), combined with low-dose radiation, can make stem cell transplants safer and more effective without traditional chemotherapy. Ideal candidates for this trial include those experiencing frequent pain crises, past strokes, or other serious complications from sickle cell disease, and who have a fully matched sibling willing to donate stem cells. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

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

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

Research has shown that the treatments tested in this trial have been safe in past studies. Alemtuzumab, used in some stem cell transplants, was well-tolerated, with most patients not experiencing serious side effects.

For the non-myeloablative stem cell transplant, studies have found it to be generally safe for people with sickle cell disease. There is a small chance, about 14.4%, of graft failure, where the new stem cells might not work as expected. This risk is known but relatively low.

Sirolimus, another medication used in the trial, has been safe in various studies. It is often used to help manage sickle cell disease and has shown benefits without major side effects. However, all treatments can have some risks, and each patient's experience may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for sickle cell disease, such as hydroxyurea or blood transfusions, the approach of combining alemtuzumab, allogeneic non-myeloablative stem cell transplantation, and sirolimus offers a novel way to tackle this condition. Researchers are excited because this method aims to replace the faulty blood-forming stem cells with healthy ones from a donor, potentially offering a more permanent solution. Alemtuzumab helps by preparing the body to accept the new cells, while sirolimus is used to maintain the new stem cells without the harsh effects of traditional chemotherapy. This approach could lead to long-term relief from the disease, offering hope for a cure rather than just managing symptoms.

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

Research has shown that less intense stem cell transplants, such as the Allogeneic Non-Myeloablative Stem Cell Transplantation studied in this trial, can be effective for individuals with severe sickle cell disease (SCD). Specifically, studies found that about 91% of patients who received this treatment survived and no longer required regular blood transfusions. Using a fully matched sibling as a donor reduces the risk of complications. This method employs low-dose radiation and medications like Alemtuzumab and Sirolimus to suppress the immune system, making it suitable for patients who cannot tolerate stronger treatments. Overall, these transplants offer a promising option for treating sickle cell disease in some patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Damiano Rondelli, MD

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

This trial is for individuals aged 16-60 with aggressive sickle cell disease who haven't responded well to or can't take hydroxyurea. Candidates must have a fully matched sibling donor, good heart and lung function, no HIV or chronic hepatitis, and be willing to sign consent. They should have had complications like frequent pain episodes, stroke, vision problems due to retinopathy, kidney issues, or severe anemia requiring transfusions.

Inclusion Criteria

Patients with sickle cell disease, subtype Hgb SS, SC, or SB disease who are on chronic transfusion therapy for a prior stroke or those patients who were intolerant of hydroxyurea therapy or were being treated with hydroxyurea therapy and were complicated by at least one of the following: Stroke or central nervous system event lasting longer than 24 hours, Frequent vaso-occlusive pain episodes, Recurrent episodes of priapism, Acute chest syndrome with recurrent hospitalizations, Red-cell alloimmunization, Bilateral proliferative retinopathy with major visual impairment in at least one eye, Osteonecrosis of 2 or more joints, Sickle cell nephropathy, Stage I or II sickle lung disease, Symptoms of pulmonary hypertension and mean pulmonary artery pressure > 25mmHg, Age 16-60 years, Karnofsky performance status of 70 or higher, Adequate cardiac function, Adequate pulmonary function, Estimated GFR ≥ 30mL/min, ALT ≤ 3x upper limit of normal, No evidence of chronic active hepatitis or cirrhosis, HIV-negative, Patient is not pregnant, History of compliance with medications and medical care, Patient is able and willing to sign informed consent, Patient has an HLA-identical matched related donor

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive alemtuzumab and low-dose total body irradiation (TBI) as part of the conditioning regimen

1 week

5 visits (in-person)

Transplantation

Participants undergo allogeneic hematopoietic stem cell transplantation

1 day

1 visit (in-person)

Post-Transplant Monitoring

Participants are monitored for engraftment and transplant-related morbidity and mortality

365 days

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alemtuzumab
• Allogeneic Non-Myeloablative Stem Cell Transplantation
• Sirolimus

Trial Overview The study tests a less harsh stem cell transplant from fully matched siblings using immune-suppressing drugs (Alemtuzumab and Sirolimus) and low-dose radiation instead of standard chemo. The goal is to see if this method helps patients accept the new cells with fewer complications.

How Is the Trial Designed?

Group I: Allogeneic Non-Myeloablative Stem Cell Transplantation Experimental Treatment 3 Interventions

The transplant regimen will consist of alemtuzumab 1mg/kg divided over five days, 300 cGy TBI, followed by sirolimus dosed for a target serum trough level of 10- 15 ng/mL.

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?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Published Research Related to This Trial

In a study involving 16 children and adolescents with sickle cell disease, a nonmyeloablative hematopoietic cell transplantation regimen showed 100% event-free and overall survival rates after a median follow-up of 19.5 months, with no observed sickling crises or graft-versus-host disease (GVHD).

All patients achieved mixed donor-recipient engraftment, indicating successful integration of donor stem cells, and sirolimus weaning was possible for most patients, suggesting a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonmyeloablative Matched Sibling Donor Hematopoietic Cell Transplantation in Children and Adolescents with Sickle Cell Disease. Guilcher, GMT., Monagel, DA., Nettel-Aguirre, A., et al.[2020]

A population pharmacokinetic model for alemtuzumab was developed using data from 206 pediatric patients, revealing that body weight significantly affects the drug's clearance and distribution, which can lead to variable drug exposure.

The study suggests that the current standard dosing method may not be optimal for all children, and individualized dosing based on this model could improve treatment outcomes and reduce toxicity associated with alemtuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome. Admiraal, R., Jol-van der Zijde, CM., Furtado Silva, JM., et al.[2023]

In a study of 10 kidney transplant recipients treated with alemtuzumab, long-term immunosuppressive therapy was found to influence the balance of T-regulatory and Th17 cells, which are important for immune response regulation.

The research demonstrated that T-regulatory cells can effectively suppress Th17 cell activity, suggesting a potential mechanism for managing immune responses in patients undergoing long-term immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Th17 cells in alemtuzumab-treated patients: the effect of long-term maintenance immunosuppressive therapy. Hester, J., Mills, N., Shankar, S., et al.[2022]

Alemtuzumab (CAMPATH-1H) is an effective monoclonal antibody for depleting T-cells in stem cell transplantation, significantly reducing the risk of graft-versus-host disease (GVHD) while maintaining low rates of graft rejection.

Current protocols for using alemtuzumab, either added to stem cell infusions or administered before transplantation, show excellent control of GVHD and have been associated with reduced transplant-related mortality, particularly from infections, although further clinical trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab in stem cell transplantation. Hale, G.[2021]

In a study of 17 pediatric patients undergoing matched unrelated hematopoietic stem cell transplantation (HSCT) with Campath-1H, the incidence of grade I-II acute graft versus host disease (GVHD) was only 29.4%, and no cases of chronic GVHD were observed, suggesting effective reduction of GVHD risk.

Despite a 35.3% relapse rate of primary disease, the overall survival rates were high at 100% at 100 days and 94% at one year, indicating that Campath-1H does not significantly increase the risk of life-threatening infections or relapse compared to conventional regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretransplant conditioning with Campath-1H (alemtuzumab) in pediatric matched unrelated hematopoietic stem cell transplants: an institutional experience. Nageswara Rao, AA., Kumar, R., Altaf, S., et al.[2017]

In a study involving 13 high-risk adult patients with sickle cell disease, a chemotherapy-free stem cell transplantation regimen resulted in successful engraftment in all patients, with 92% maintaining stable mixed donor/recipient chimerism after a median follow-up of 22 months.

The treatment showed no mortality or graft-versus-host disease, and patients experienced significant improvements in hemoglobin levels and quality of life, including aspects like bodily pain and vitality, highlighting the efficacy and safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease. Saraf, SL., Oh, AL., Patel, PR., et al.[2017]

Alemtuzumab (Campath 1H), a monoclonal antibody targeting CD52 on B and T cells, is increasingly used as a conditioning agent for bone marrow transplantation, but it can have serious side effects.

In a case study of a 37-year-old woman, acute renal failure and disseminated intravascular coagulation (DIC) occurred after receiving Campath, leading to the abortion of her transplant and ongoing dialysis, highlighting the need for caution and further investigation into its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute renal failure and disseminated intravascular coagulation following an idiosyncratic reaction to Alemtuzumab (Campath 1H) or fludarabine. Osborne, WL., Lennard, AL.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38488686/

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 ...

2. 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 ...

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

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... Graft failure (GF) estimate in sickle cell disease (SCD) patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT).

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

Clinical Outcomes Among Patients With Sickle Cell ... Among engrafted patients, 3,445 (91.1%) patients were alive and TI after allo-HSCT (Across studies: median proportion - 86.6%; range - 20.0%– ...

5. astctjournal.org astctjournal.org/article/S2666-6367(25)01168-6/fulltext

Comparison of Regimens Used for Allogeneic Matched ... We compared outcomes for SCD patients who have received HLA-matched related donor (MRD) HCT for SCD using different HCT regimens.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8582053/

Non-myeloablative human leukocyte antigen-matched related ... In summary, alemtuzumab, low-dose TBI and sirolimus were applied to the largest group of adult patients with SCD; half of them were older than 30 years old. The ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06358638

NCT06358638 | Sickle Cell Disease Transplant Using a ... Small case series have demonstrated that daratumumab is well tolerated either pre-HCT to treat patients with antibodies against mismatched donor HLA antigens, ...

8. astctjournal.org astctjournal.org/article/S1083-8791(19)30136-3/fulltext

Nonmyeloablative Matched Sibling Donor Hematopoietic ... All recipients tolerated the conditioning regimen well, with no grade 3 or 4 reactions to alemtuzumab. The median length of hospital stay was 7 days from stem ...

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

Comparison of outcomes following subcutaneous or ... Subcutaneous administration of alemtuzumab for children undergoing transplant for sickle cell disease is safe and effective. Introduction. Alemtuzumab is a ...

10. researchgate.net researchgate.net/publication/281621630_Non-Myeloablative_Stem_Cell_Transplant_with_AlemtuzumabLow_Dose_Irradiation_to_Cure_and_Improve_the_Quality_of_Life_of_Adults_with_Sickle_Cell_Disease

Non-Myeloablative Stem Cell Transplant with ... Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely performed in adult patients with sickle cell disease (SCD).