Stem Cell Transplants for Sickle Cell Disease and Thalassemia

Overseen By Ashish Gupta, MBBS, MPH

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Pregnancy, HIV, Uncontrolled infection, 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

Duration: 6-8 weeks

62 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of stem cell transplants for treating sickle cell disease and other blood disorders that require regular transfusions. Participants will receive a stem cell transplant from matched siblings or unrelated donors to determine if this can reduce or eliminate their need for transfusions. Individuals with conditions like sickle cell disease or thalassemia who depend on frequent blood transfusions might be suitable candidates for this study. The trial will test different transplant methods, including allogeneic hematopoietic stem cell transplantation, to identify the best approach for these conditions. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants the chance to benefit from potentially groundbreaking therapies.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team to get a clear answer.

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

Research has shown that allogeneic hematopoietic stem cell transplantation (HSCT) has been studied in individuals with sickle cell disease and other blood disorders. One study found that when performed at a young age, over 90% of patients with sickle cell disease lived without the disease afterward. Another study reported that 94% of patients survived for at least two years post-procedure. However, serious complications, such as infections, can occur and pose significant risks.

The treatment's safety depends on various factors, including the type of donor and the body's preparation for the transplant. While these treatments show promise, the risk of complications necessitates a careful evaluation of benefits and risks. Prospective clinical trial participants should discuss these factors with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of allogeneic hematopoietic stem cell transplantation for treating sickle cell disease and thalassemia because it offers a potentially curative approach, unlike standard treatments that mainly manage symptoms. This method involves replacing the patient's defective blood-forming cells with healthy ones from a donor, which can result in the complete elimination of the disease-causing cells. The trial explores various donor matches, including sibling and unrelated donors, and even mismatched donors, offering hope for a wider range of patients who may not have a perfect match. These approaches provide a unique opportunity to assess the effectiveness and safety of different donor regimens, potentially expanding treatment options for these genetic blood disorders.

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

This trial will evaluate the effectiveness of different donor stem cell transplant regimens for treating sickle cell disease and thalassemia. Studies have shown that donor stem cell transplants effectively treat these conditions. Specifically, research indicates that patients with sickle cell disease experienced fewer pain episodes and improved quality of life after receiving these transplants compared to standard treatments. A review of studies found that 94% of patients survived after undergoing this treatment. For thalassemia, stem cell transplants can cure, especially for children with severe cases. The evidence strongly supports stem cell transplants as a promising treatment option for these blood disorders. Participants in this trial will be assigned to one of the various treatment arms, each exploring different donor and conditioning regimens. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with severe blood disorders like Sickle Cell Disease and Thalassemia, who haven't found relief through other treatments. Participants must be willing to use effective contraception and have a matched sibling donor for the transplant. They should be in relatively stable health (Karnofsky score ≥ 60%) but exceptions may be made after team evaluation.

Inclusion Criteria

Sexually active persons of childbearing potential or persons with partners of childbearing potential must agree to use a highly effective form of contraception during study treatment and for at least 4 months after the transplant.

I have Diamond Blackfan Anemia.

I have a blood disorder that is not cancer.

Exclusion Criteria

Pregnant, breastfeeding or intending to become pregnant during the study. Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days of the start of treatment

HIV Positive

Known allergy to any of the study components

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo allogeneic hematopoietic stem cell transplantation (HSCT) with various regimens based on donor matching

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness, including survival and GvHD outcomes

2 years

Open-label extension (optional)

Participants may continue to be monitored for long-term outcomes beyond the initial follow-up period

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation

Trial Overview The study tests a combination of drugs (like Tacrolimus, Thiotepa) and procedures (Total Body Irradiation, Stem Cell Transplant) to treat high-risk hemoglobinopathies using donor stem cells. It's an open-label phase II trial, meaning everyone gets the treatment and knows what it is.

How Is the Trial Designed?

Group I: Arm D Experimental Treatment 8 Interventions

Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI

Group II: Arm C Experimental Treatment 6 Interventions

Arm C Fully Matched unrelated donor (MUD)- - 0-55 years; ATG/Flu/Bu

Group III: Arm B Experimental Treatment 6 Interventions

Arm B Matched sib regimen - 0-55 (per physician preference for patients over 6) ATG/Flu/Bu

Group IV: Arm A Experimental Treatment 5 Interventions

Arm A Matched sib regimen - Age 6 -55 (per physician preference for patients over 6) Campath/TBI

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

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/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% ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/5/955/525812/Hematopoietic-cell-transplant-compared-with

Hematopoietic cell transplant compared with standard care in ... Patients with SCD experienced fewer pain crises and improved patient-reported outcomes after HCT when compared with standard care. Subjects:.

4. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1036939/full

Allogeneic hematopoietic stem cell transplantation to cure ... The overall survival and event-free survival at 4 years were 91% and 73%, respectively (75). After 10 years of his first report, Vermylen et al.

5. aetna.com aetna.com/cpb/medical/data/600_699/0626.html

Hematopoietic Cell Transplantation for Thalassemia Major ... Hsieh and colleagues (2014) stated that myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell ...

6. astctjournal.org astctjournal.org/article/S2666-6367(25)01447-2/fulltext

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... Subgroup analysis demonstrated that clinical outcomes varied based on the type of donors, conditioning procedures/regimens and stem cell sources ...

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

Is allogeneic transplantation for sickle cell disease still ... Five participants died from infectious complications for an overall 2-year event-free survival (EFS) of 83% and an overall survival (OS) of 94%.

8. 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 ...

9. cms.gov cms.gov/medicare/coverage/evidence/stem-cell-transplant-sickle-cell

Allogeneic Hematopoietic Stem Cell Transplant for Sickle ... Allogeneic HSCT for sickle cell disease (SCD) will be covered by Medicare only for beneficiaries with severe, symptomatic sickle cell disease.