Stem Cell Transplant for Sickle Cell Disease

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Columbia University

Disqualifiers: Pregnant, Infections, Liver 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: 30

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if lower doses of chemotherapy can effectively replace bone marrow and control sickle cell disease with fewer side effects. Participants will receive chemotherapy, including drugs such as Alemtuzumab (Campath, Lemtrada, or MabCampath), Busulfan (Busulfex or Myleran), and Fludarabine (Fludara or Oforta), followed by a stem cell transplant from a matched donor. The trial targets individuals with sickle cell disease who have a matched sibling or unrelated donor and experience chronic anemia with low hemoglobin. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in sickle cell treatment.

Do I have to stop taking 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 trial coordinators or your doctor.

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

Research has shown that a combination of busulfan, fludarabine, and alemtuzumab for stem cell transplants has some safety data. This treatment can be effective for blood disorders like sickle cell disease, but it carries a risk of serious side effects. Some studies report a 5-10% chance of transplant-related mortality, indicating a small risk of death from the procedure itself.

Alemtuzumab prepares the body for new stem cells by blocking certain immune responses. Busulfan and fludarabine, types of chemotherapy, help the body accept the new stem cells. These drugs have been used before and are generally well-tolerated, though reports of side effects like graft failure, where the new cells do not grow as expected, exist.

Overall, this treatment is considered to have reduced toxicity, making it less harsh on the body compared to other methods. However, like any medical treatment, risks are involved. Patients considering joining the trial should weigh these risks against the potential benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Sickle Cell Disease, which often include hydroxyurea or blood transfusions, this investigational approach uses an allogeneic stem cell transplant. What makes this treatment unique is its potential to address the underlying cause of the disease by replacing the patient's defective stem cells with healthy ones from a donor. Researchers are excited about this treatment because it offers the possibility of a long-term cure rather than just managing symptoms, which is a significant advancement in the field. Additionally, the use of chemotherapy agents like Alemtuzumab, Busulfan, and Fludarabine in combination aims to optimize the transplant process, potentially increasing the success rate of the procedure.

What evidence suggests that this trial's treatments could be effective for Sickle Cell Disease?

Research has shown that a stem cell transplant from a donor can effectively treat sickle cell disease. In this trial, participants in the SCD group will receive chemotherapy with Busulfan, Fludarabine, and Alemtuzumab before undergoing an allogeneic stem cell transplant. Studies indicate that about 94% of patients survive, with many experiencing long-term symptom relief. Alemtuzumab, used in this treatment, has demonstrated good results with high survival rates and no serious side effects like graft-versus-host disease, where donor cells attack the patient's body. When combined with Busulfan and Fludarabine, which prepare the body for the transplant, these treatments have led to successful and lasting outcomes for many patients. The evidence suggests a promising way to manage sickle cell disease with fewer complications. ^{6 7 8 9 10}

Who Is on the Research Team?

Monica Bhatia, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for individuals under 30 years old with severe forms of blood disorders like Sickle Cell Disease or Thalassemia, who haven't responded well to other treatments. They need a matched stem cell donor, good kidney and liver function, heart and lung health, and can't be pregnant or have uncontrolled infections.

Inclusion Criteria

Age ≤30

Diagnosis of Homozygous Hemoglobin S Disease or Heterozygous Hemoglobin Sickle Cell (SC) or S 0/+ thalassemia, or Sickle/variant resulting in Chronic Hemolytic Anemia with hemoglobin (HgB) ≤10 mg/dL

Matched sibling donor and asymptomatic, or 8/8 human leukocyte antigen (HLA) matched unrelated adult donor

Exclusion Criteria

Evidence of uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms) within 1 month prior to starting the conditioning regimen. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.

Karnofsky/Lansky Performance Score <60%

Histologic Exam of Liver (liver biopsy) with bridging fibrosis or cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive a chemotherapy regimen with busulfan, fludarabine, and alemtuzumab

4-6 weeks

Multiple visits for chemotherapy administration

Stem Cell Transplant

Participants undergo allogeneic stem cell transplant

1 week

Inpatient stay for transplant procedure

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Regular follow-up visits at Day 30, 60, 100, 180, 1 year, 2 years, 3 years, 5 years, 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Alemtuzumab
• Allogeneic stem cell transplant
• Busulfan
• Fludarabine

Trial Overview The study tests if lower doses of chemotherapy (busulfan, fludarabine) followed by alemtuzumab and a stem cell transplant from a related or unrelated donor can effectively treat the disease with fewer harsh side effects.

How Is the Trial Designed?

Group I: SCD group Experimental Treatment 4 Interventions

Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.

Group II: BT group Experimental Treatment 4 Interventions

Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.

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?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33534948/

outcomes from three independent centres - PubMed - NIH Overall and sickle-free survival at one and five years were 93% and 85% respectively. Age, sex, pre-HPCT sickle complications, ferritin and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06358638

NCT06358638 | Sickle Cell Disease Transplant Using a ... This is a phase 2 study given that the studied nonmyeloablative conditioning backbone (alemtuzumab, 300 cGY TBI, sirolimus) has been previously used effectively ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1083879115005972

Adult Nonmyeloablative Stem Cell Transplantation with ... No treatment-related mortality or graft-versus-host disease occurred after alemtuzumab/total body irradiation conditioning in sickle cell disease adults.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9338787/

Alemtuzumab clearance, lymphocyte count, and T-cell ... Between 2 and 4 months after transplant, higher alemtuzumab levels measured 14 days after transplant correlated with patients having better engraftment.

5. link.springer.com link.springer.com/article/10.1007/s00277-023-05447-4

Excellent outcome of stem cell transplantation for sickle ... The disease-free, severe GVHD-free survival was 100%, 100%, and 80% in the MFD, MUD, and MMFD groups, respectively (p = 0.106). There was a ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00301834

Alemtuzumab, Fludarabine, and Busulfan Followed By ... RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread.

7. astctjournal.org astctjournal.org/article/S1083-8791(12)00641-6/fulltext

Reduced Toxicity Conditioning with Busulfan, Fludarabine ... However, this approach is limited by 5-10% transplant-related mortality, 5-10% primary graft failure and the late effects of Bu/CY. Alternate approaches include ...

8. 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 ...

9. astctjournal.org astctjournal.org/article/S2666-6367(23)01469-0/fulltext

Myeloablative Dose of Busulfan and Fludarabine ... Myeloablative dose of Busulfan and Fludarabine combined with in vivo T cell depletion is safe and effective conditioning for acute myeloid leukemia and ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24797180/

Reduced toxicity, myeloablative conditioning with BU, ... We investigated in a prospective single institutional study, the safety and efficacy of a reduced-toxicity conditioning (RTC) regimen of BU 12.8-16 mg/kg, ...