What side effects are associated with this type of intervention?

Common treatments for Sickle Cell Disease, such as gene therapy and hydroxyurea, have specific side effects. Gene therapy, particularly involving the modification of BCL11A to increase fetal hemoglobin, may involve risks related to chemotherapy used for conditioning, such as infections, bleeding, and organ toxicity. Hydroxyurea can cause bone marrow suppression, leading to lower white blood cell and platelet counts, increasing the risk of infections and bleeding. Other side effects of hydroxyurea include gastrointestinal disturbances, skin and nail changes, and potential long-term risks like secondary malignancies.

What prior FDA approvals exist?

Hydroxyurea is the most established FDA-approved treatment for Sickle Cell Disease, known for its efficacy in reducing vaso-occlusive pain and other complications by increasing fetal hemoglobin (HbF) levels. While gene therapy targeting BCL11A to increase HbF is still under investigation, hydroxyurea remains the primary treatment with the longest track record of safety and effectiveness. Other treatments, such as chronic transfusions and hematopoietic cell transplantation, are also used but are not directly comparable to the gene therapy approach being studied.

What other types of research exist?

Promising, novel alternatives to gene therapy for Sickle Cell Disease patients include: 1) Hydroxyurea, which is recommended as the first-line therapy for reducing vaso-occlusive pain and other complications, with extensive safety and efficacy data. 2) Chronic red blood cell transfusions, which can prevent complications such as stroke and manage severe anemia, though they carry risks like alloimmunization and iron overload. 3) Hematopoietic cell transplantation, which can be curative, especially in children, though it requires a matched donor and carries risks of graft-versus-host disease. These alternatives should be discussed with a healthcare provider to determine the best individualized treatment plan.

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Gene Therapy

Gene Therapy for Sickle Cell Disease (GRASP Trial)

Phase 2

Recruiting

Research Sponsored by David Williams

Eligibility Criteria Checklist

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

Must have

Age between 13-40 years

Clinically severe disease, defined as at least 4 vaso-occlusive events (VOEs) within the past 24 months prior to consent

Must not have

Prior allogeneic hematopoietic stem cell transplant

History of abnormal TCD and transitioned to hydroxyurea

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months prior to consent and 6 months to 24 months post-infusion of gene modified cells

Awards & highlights

No Placebo-Only Group

Summary

This trial uses gene therapy to treat patients with severe Sickle Cell Disease by modifying their own blood stem cells. The treatment aims to increase healthy hemoglobin levels by changing a specific gene. This approach could reduce painful episodes and improve overall health without needing a donor.

Who is the study for?

This trial is for people aged 13-40 with severe sickle cell disease (HbSS or HbS/β0 thalassemia) who've had at least 4 pain crises in the last 2 years. They need good organ function, no matching bone marrow donor, and can't be on chronic blood transfusions or have a history of stroke, certain infections like HIV/Hepatitis, liver issues from iron overload, or other conditions that could interfere with treatment.

What is being tested?

The study tests gene therapy to increase fetal hemoglobin which doesn't sickle. Patients' own stem cells are modified using a virus vector targeting BCL11A gene to reduce sickling hemoglobin levels. This could potentially cure or improve their condition without needing a donor and may use less chemotherapy.

What are the potential side effects?

Potential side effects include those related to chemotherapy used before transplanting the modified cells back into patients such as nausea, hair loss, increased infection risk; and any unknown risks associated with the new gene therapy approach.

Eligibility Criteria

Inclusion Criteria

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

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I am between 13 and 40 years old.

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I have had 4 or more severe pain episodes in the last 2 years.

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I don't have a family member who is a perfect match for a bone marrow donation.

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I have sickle cell disease with either HbSS or HbS/β0 thalassemia genotype.

Exclusion Criteria

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

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I have had a stem cell transplant from a donor.

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I have an abnormal TCD history and am now on hydroxyurea.

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I have severe blood vessel problems in my brain.

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I have recurring priapism that hasn't improved with treatment.

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I am on a regular transfusion plan to prevent strokes.

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I have a known bone marrow disorder or abnormal bone marrow cells.

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I cannot take busulfan due to health reasons.

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I have had a stroke or a neurological event that lasted more than a day.

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I have a genetic condition that causes blood clots or I've had a blood clot before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months prior to consent and 6 months to 24 months post-infusion of gene modified cells

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months prior to consent and 6 months to 24 months post-infusion of gene modified cells

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months prior to consent and 6 months to 24 months post-infusion of gene modified cells for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Occurrence of VOEs by Month 24 post-infusion

Secondary study objectives

Hemoglobin Function

Hemolysis

Occurrence of VOEs by Month 18 post-infusion

+2 more

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: Treatment ArmExperimental Treatment1 Intervention

Open-label, non-randomized, single arm study of a single infusion of autologous CD34+ HSC cells transduced with the lentiviral vector containing a shRNA targeting BCL11a.

0 / 13Eligibility 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

Common treatments for Sickle Cell Disease (SCD) include gene therapy, hydroxyurea, and blood transfusions. Gene therapy, such as the modification of BCL11A, increases fetal hemoglobin (HbF) production, which does not sickle and reduces the proportion of sickle hemoglobin (HbS) in red blood cells. Hydroxyurea also increases HbF levels, reducing the frequency of painful vaso-occlusive episodes and other complications. Blood transfusions dilute the concentration of HbS, decreasing sickling events and related complications. These treatments are vital for SCD patients as they address the disease's root cause, aiming to alleviate symptoms, prevent complications, and enhance quality of life.

Gene therapy for sickle cell disease.Gene therapy for sickle cell disease.