Nonmyeloablative Stem Cell Transplant for Sickle Cell Anemia and Thalassemia

Not currently recruiting at 1 trial location

Overseen By Matthew M Hsieh, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Disqualifiers: Uncontrolled infections, Major illness, Pregnancy, 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: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help individuals with sickle cell disease or beta-thalassemia better accept stem cell transplants. Researchers test a combination of low-dose radiation and specific drugs, such as cyclophosphamide and sirolimus, to determine if they improve transplant success. Participants should have sickle cell disease or beta-thalassemia with severe complications or organ damage that current treatments cannot improve. The trial involves both patients and their matching family donors. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in treatment.

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 combining low-dose radiation with the drugs cyclophosphamide, pentostatin, and sirolimus is generally safe for patients. In one study using this combination, most patients responded well, and many successfully received new stem cells. This treatment helps the body accept new stem cells more easily.

In another study on sickle cell disease, 95% of participants were alive two years after receiving similar stem cell transplants, and 88% did not experience a return of their disease. These results suggest that the treatment is quite safe, with strong survival rates.

While all medical treatments carry risks, these findings indicate that the treatment in this trial has a good safety record based on past experiences. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the nonmyeloablative stem cell transplant for sickle cell anemia and thalassemia because it offers a less intense alternative to traditional bone marrow transplants, which typically require more aggressive conditioning. This protocol uses a combination of drugs like cyclophosphamide, pentostatin, and sirolimus to prepare the body and help reduce the risk of complications. Additionally, the approach of using male donors for female participants or addressing pre-existing antibodies adds a personalized touch that could improve outcomes. This innovative method could make stem cell transplants safer and more accessible for patients with these genetic blood disorders.

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

This trial will evaluate the effectiveness of combining low-dose radiation with three specific drugs—cyclophosphamide, pentostatin, and sirolimus—to help the body accept donor stem cells more easily. Research has shown that one year after this treatment, 95% of patients remained alive. This approach also reduced the risk of the body attacking the new cells from 44% to just 5%. These results are promising for using stem cell transplants to treat sickle cell disease and beta-thalassemia. ^{1 6 7 8 9}

Who Is on the Research Team?

Matthew M Hsieh, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is for people aged 4 and older with severe sickle cell disease or beta-thalassemia, who are at high risk of complications not improved by other treatments. They must have a matched family donor willing to donate stem cells. Exclusions include serious infections within the last month, pregnancy, lactation, or any major illness that could interfere with transplant survival.

Inclusion Criteria

I am at least 4 years old.

I am eligible for hydroxyurea treatment or a stem cell transplant.

Negative beta-HCG, when applicable

Exclusion Criteria

I do not have any major illnesses or organ failures that would make a stem cell transplant impossible.

I need considerable assistance and am unable to carry out any work activities.

Evidence of uncontrolled bacterial, viral, or fungal infections within one month prior to starting the conditioning regimen

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-Transplant Conditioning

Participants receive low dose radiation and immunosuppressive drugs to prepare for stem cell transplant

3 weeks

Multiple visits (in-person)

Transplantation

Participants receive donor stem cells via IV infusion

1 day

1 visit (in-patient)

Post-Transplant Recovery

Participants remain in the hospital for recovery and monitoring

30 days

In-patient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Weekly visits (outpatient clinic) for 4 months, then regular follow-ups

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Pentostatin
• Radiotherapy
• Sirolimus

Trial Overview The study tests a new transplant method using low-dose radiation and immunosuppressive drugs (cyclophosphamide, pentostatin, sirolimus) to see if they help patients better accept donated stem cells. Participants will undergo various procedures including blood tests and bone marrow sampling before receiving the treatment in hospital.

How Is the Trial Designed?

Group I: Participants with pre-existing antibodies and SCD or Beta-thalassemia receiving stem cell transplant Experimental Treatment 5 Interventions

Participants with pre-existing antibodies and Sickle Cell Disease (SCD) or Beta-thalassemia receiving stem cell transplant. Pentostatin given on days -21, -17, -13, -9 and oral cyclophosphamide from days -21 to -8, with the intention to be administered in the outpatient setting. Alemtuzumab on days 7 to 3, and 300 cGy TBI on day 2. Sirolimus started at a loading dose of 5mg PO every 4 hours for three doses on day -1 and adjusted to maintain trough levels between 10-15 ng/mL. The PBSC graft targeted to deliver .10 x 106 CD34+ cells/kg (minimum .5 x 106) and infused on day 0.

Group II: Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor Experimental Treatment 1 Intervention

Participants received filgrastim to mobilize peripheral blood stem cells for apheresis collection. Collected stem cells of donor will then be infused to HLA matched sibling.

Group III: Female participants with SCD or Beta-thalassemia receiving stem cell transplant with male donor Experimental Treatment 5 Interventions

Female participants with Sickle Cell Disease (SCD) or Beta-thalassemia receiving stem cell transplant with male donor. Pentostatin given on days -21, -17, -13, -9 and oral cyclophosphamide from days -21 to -8, with the intention to be administered in the outpatient setting. Alemtuzumab on days 7 to 3, and 300 cGy TBI on day 2. Sirolimus started at a loading dose of 5mg PO every 4 hours for three doses on day -1 and adjusted to maintain trough levels between 10-15 ng/mL. The PBSC graft targeted to deliver .10 x 106 CD34+ cells/kg (minimum .5 x 106) and infused on day 0.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

National Institutes of Health Clinical Center (CC)

Collaborator

Trials

391

Recruited

30,880,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase I study involving 9 patients with advanced hematological malignancies, the combination of cytosine arabinoside (Ara-C) and cyclophosphamide (CY) with total body irradiation (TBI) resulted in severe toxicity, with multiple patients experiencing fatal outcomes at higher doses.

The study concluded that the concurrent administration of Ara-C and CY may not be suitable for phase I trials due to the high risk of severe, dose-independent toxicity, highlighting the need for caution in developing such treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous infusion of high-dose cytosine arabinoside with cyclophosphamide followed by total body irradiation and marrow infusion for the treatment of patients with advanced hematological malignancy. Petersen, FB., Appelbaum, FR., Buckner, CD., et al.[2016]

High doses of cyclophosphamide (CY) can be toxic to bone marrow, but when combined with autologous marrow transplantation, it allows for recovery from severe side effects, as shown in dog studies where 100 mg/kg was lethal without support but manageable with marrow infusion.

In human patients, conditioning with CY (50 mg/kg) before allogeneic marrow transplantation for severe aplastic anemia has resulted in an 80% long-term survival rate, demonstrating the efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose therapy and bone marrow transplantation. Thomas, ED.[2018]

In a study of 58 patients with hematologic malignancies, a myeloablative regimen combining high-dose cytosine arabinoside (ara-C), cyclophosphamide, and total body irradiation (TBI) demonstrated a 1-year survival rate of 69% and a 5-year survival rate of 54%.

The regimen showed a low relapse rate of only 7% after a median follow-up of 28 months, suggesting that the combination of these treatments is both safe and effective, potentially due to the additional antileukemic effects of ara-C.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclophosphamide, cytosine arabinoside and TBI as a conditioning regimen for allogeneic bone marrow transplantation in patients with leukemia. Jillella, AP., Doria, R., Khan, K., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12424894/

Nonmyeloablative Pentostatin-Cyclophosphamide ... One-year overall survival was 95%; in the first year, there was 1 death on each protocol. Table 2 summarizes the post-HCT outcomes. At one-year post-HCT, there ...

2. medrxiv.org medrxiv.org/content/10.1101/2025.08.31.25334807v1.full.pdf

Nonmyeloablative Pentostatin-Cyclophosphamide ... sickle cell anemia who underwent haploidentical peripheral blood stem cell. 516 transplantation. Bone Marrow Transplant, 2017. 52(4): p. 641 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40950459/

Nonmyeloablative Pentostatin-Cyclophosphamide ... - PubMed One-year overall survival was 95%. The PC regimen was associated with a reduction in acute rejection one-year post-HCT (5% vs. 44%; p=0.004) and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02105766

NCT02105766 | Nonmyeloablative Peripheral Blood ... - To see if low dose radiation (300 rads), oral cyclophosphamide, pentostatin, and sirolimus help a body to better accept donor stem cells. Eligibility: - ...

5. astctjournal.org astctjournal.org/article/S2666-6367(25)01055-3/fulltext

Two Nonmyeloablative HLA-Matched Related Donor ... Two nonmyeloablative HLA-matched related donor allogeneic hematopoietic cell transplantation regimens in patients with severe sickle cell disease.

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT02105766

NCT02105766 | Nonmyeloablative Peripheral Blood ... Eligibility: - People 4 and older with beta-thalassemia or sickle cell disease that can be cured with transplant, and their donors. Design:

7. 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- ...

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

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... This systematic review and meta-analysis present strong evidence for the safety and efficacy of allo-HSCT in SCD treatment, with an OS of 94% ...

9. hopkinsmedicine.org hopkinsmedicine.org/news/newsroom/news-releases/2023/12/a-cure-for-sickle-cell-disease

A Cure for Sickle Cell Disease Of the 42 participants, 95% were still alive two years after transplant, and 88% have not seen their sickle cell disease return and are ...