What side effects are associated with this type of intervention?

Common treatments for Sickle Cell Disease (SCD) include hydroxyurea, chronic transfusion therapy, and hematopoietic stem cell transplantation (HSCT). Hydroxyurea can cause bone marrow suppression, leading to neutropenia, thrombocytopenia, and anemia. Chronic transfusion therapy carries risks such as iron overload, alloimmunization, and transfusion reactions. HSCT, especially with HLA-identical sibling donors, can result in graft-versus-host disease (GVHD), infections due to immunosuppression, and organ toxicity. The trial using alemtuzumab, low dose total-body irradiation, and sirolimus aims to minimize these toxicities while achieving a high cure rate.

What prior FDA approvals exist?

Hydroxyurea is a key FDA-approved treatment for Sickle Cell Disease, effective in reducing painful episodes and other complications. Chronic transfusion therapy is also used, especially for stroke prevention. Hematopoietic stem cell transplantation (HSCT) offers a potential cure and involves immune modulation and myelosuppression, similar to the trial using alemtuzumab, low dose total-body irradiation, and sirolimus. Ongoing research and clinical trials continue to explore new treatments, including gene therapy.

What other types of research exist?

Promising novel alternatives for Sickle Cell Disease treatment in 2024 include gene therapy approaches such as CRISPR-Cas9 mediated gene editing and lentiviral vector-based gene addition. Additionally, newer pharmacological agents like voxelotor (which increases hemoglobin's affinity for oxygen) and crizanlizumab (a monoclonal antibody targeting P-selectin to reduce vaso-occlusive crises) are showing potential. Alternative transplantation methods, such as haploidentical transplantation with post-transplant cyclophosphamide, are also being explored to reduce toxicity and expand donor availability.

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Monoclonal Antibodies

Transplant Method for Sickle Cell Disease (SUN Trial)

Phase 2

Recruiting

Led By Rober Nickel, MD

Research Sponsored by Robert Nickel

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

- Administration of regular RBC transfusions (≥8 transfusions in the previous 12 months).

- History of two or more episodes of acute chest syndrome (ACS) in lifetime.

Must not have

- Infection Disease: Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning. Patients with confirmed seropositivity for HIV and patients with active Hepatitis B or C determined by serology and/or NAAT are excluded.

- Pulmonary function: Diffusion capacity of carbon monoxide (DLCO) <35% (adjusted for hemoglobin). Baseline oxygen saturation <85% or PaO2 <70.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day +30, and day +100 post transplant

Awards & highlights

No Placebo-Only Group

Summary

This trial uses a combination of drugs and mild radiation to help children with sickle cell disease receive treatment from a sibling. It aims to reduce side effects while maintaining high cure rates. The focus is on children who need a safer treatment option.

Who is the study for?

This trial is for children with Sickle Cell Disease who have had complications like stroke, frequent pain or acute chest syndrome despite treatment. They must not have severe liver, heart, kidney, lung problems or a history of certain blood reactions and should not be pregnant.

What is being tested?

The study tests a transplant method using alemtuzumab (an antibody), low dose radiation, and sirolimus (an immune system regulator) in siblings with matching tissue types to treat SCD with potentially less toxicity than traditional methods.

What are the potential side effects?

Possible side effects include weakened immune response leading to infection risk, potential liver issues from alemtuzumab, mouth sores or skin rashes from sirolimus, and fatigue or nausea from radiation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have received 8 or more blood transfusions in the last year.

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I have had two or more episodes of severe chest pain in my life.

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I have had two or more acute coronary syndrome episodes in the last 2 years.

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I've needed strong pain medication for sickle cell pain more than three times in the last year.

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I'm sorry, but you seem to have provided an incomplete sentence. Please provide the full criterion you would like me to rewrite.

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I have had a stroke.

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I have been hospitalized for sickle cell pain or acute chest syndrome while on hydroxyurea.

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I have had 3 or more severe pain episodes from sickle cell disease treated with strong painkillers.

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I have had two or more long-lasting erections needing urgent care.

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I've had at least two episodes where my spleen trapped blood cells, requiring transfusions or surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any uncontrolled infections or active Hepatitis B/C or HIV.

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My lung function is severely reduced.

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My heart's pumping ability is below the normal range.

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My kidney function is reduced with a creatinine clearance below 60 mL/min.

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My liver tests show bilirubin > 1.5 mg/dL and transaminases >5 times the normal limit.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day +30, and day +100 post transplant

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day +30, and day +100 post transplant

This trial's timeline: 3 weeks for screening, Varies for treatment, and day +30, and day +100 post transplant for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Acute GVHD

Secondary study objectives

PedsQL 4.0 Measurement model for the Pediatric Quality of Life Inventory

Other study objectives

Patient-Reported Outcomes Measurement Information System (PROMIS)

Platelet transfusion

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: SUN regimenExperimental Treatment1 Intervention

Alemtuzumab, low dose total body irradiation, Sirolimus HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus (Sickle transplant Using a Nonmyeloablative approach, "SUN") can decrease the toxicity of transplant while achieving a high cure rate for children with sickle cell disease (SCD).

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Sickle Cell Disease (SCD) include hydroxyurea, red blood cell transfusions, and HLA-identical sibling donor transplantation. Hydroxyurea increases fetal hemoglobin (Hb F) production, reducing red blood cell sickling and vaso-occlusive events. Red blood cell transfusions provide normal red blood cells to improve oxygen delivery and reduce complications like stroke. HLA-identical sibling donor transplantation, using alemtuzumab (lymphocyte depletion), low dose total-body irradiation (immune response reduction), and sirolimus (mTOR inhibition), aims to replace defective bone marrow with healthy marrow, reducing sickled cell production. These treatments are vital as they address the root causes of SCD, alleviating pain, preventing complications, and enhancing patients' quality of life.