What side effects are associated with this type of intervention?

Common treatments for Sickle Cell Anemia include hydroxyurea, chronic transfusion therapy, and hematopoietic stem cell transplantation (HSCT). Hydroxyurea can cause myelosuppression, leading to neutropenia, thrombocytopenia, and anemia. Chronic transfusion therapy may result in iron overload and alloimmunization. HSCT, particularly with T-cell depletion to reduce graft-versus-host disease (GVHD), carries risks such as infection, graft failure, and other transplant-related complications.

What prior FDA approvals exist?

The FDA has approved several treatments for Sickle Cell Anemia, including hydroxyurea, which reduces the frequency of pain crises and the need for blood transfusions. Chronic transfusion therapy is another standard treatment to prevent complications such as stroke. Hematopoietic cell transplantation, particularly from matched sibling donors, is considered a curative option. Recent studies are investigating the use of mismatched unrelated volunteer donor and haploidentical related donor stem cell transplants with T-cell depletion to reduce graft-versus-host disease, potentially expanding the pool of eligible transplant recipients.

What other types of research exist?

Promising novel alternatives for treating sickle cell anemia in 2024 include: 1) Hydroxyurea, which is recommended for its efficacy in reducing vaso-occlusive pain and improving survival; 2) Chronic transfusion therapy, which is effective for stroke prevention but requires management of iron overload; 3) Investigational agents, which are being explored for their potential benefits; and 4) Hematopoietic cell transplantation (HCT) from matched related donors, which has shown success in reducing stroke risk and stabilizing neurologic abnormalities.

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Cell Therapy

Bone Marrow Transplant for Sickle Cell Disease

Phase 1 & 2

Recruiting

Led By Paul Szabolcs, MD

Research Sponsored by Paul Szabolcs

Eligibility Criteria Checklist

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

Must have

Agreement to use FDA approved birth control for specified duration

Ages 5 years to 40 years, at time of consent

Must not have

Patients who have undergone stem cell transplantation in the 6 months prior to anticipated conditioning

Patients with uncontrolled bacterial, viral or fungal infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline through study completion, an average of 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial uses stem cells from mismatched donors with certain immune cells removed to treat patients with severe blood disorders who lack a perfect donor match. The approach aims to replace damaged cells, reduce complications, and support recovery with additional immune cells. A new technique has been developed to improve the treatment process.

Who is the study for?

This trial is for people aged 5-40 with severe sickle cell disease or other anemias needing many blood transfusions and showing organ damage. They must have tried Hydroxyurea without success, not be pregnant, HIV negative, and agree to birth control post-transplant. A suitable donor match is also required.

What is being tested?

The study tests if stem cell transplants from mismatched unrelated or related donors can help treat severe sickle cell disease and other anemias requiring frequent transfusions. It aims to reduce graft-versus-host disease using a T-cell depleted method in the transplant process.

What are the potential side effects?

Potential side effects may include immune system reactions due to the depletion of T-cells, infusion-related reactions from drugs like Alemtuzumab, Rituximab, Fludarabine; as well as possible organ toxicity from Thiotepa.

Eligibility Criteria

Inclusion Criteria

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

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I agree to use approved birth control methods for the required time.

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I am between 5 and 40 years old.

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I have Sickle Cell Disease or beta-thalassemia with complications or need regular blood transfusions.

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My donor is a match for me.

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I have tried hydroxyurea for my sickle cell disease, but it didn't work.

Exclusion Criteria

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

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I had a stem cell transplant less than 6 months ago.

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I do not have any uncontrolled infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline through study completion, an average of 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline through study completion, an average of 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline through study completion, an average of 2 years 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 Graft versus host disease

Bone Transplantation

Graft rejection

+1 more

Secondary study objectives

Adult Sickle Cell Quality of Life Measurement System (ASCQ)

Cytomegalovirus (CMV) infection

Donor Cell Engraftment

+11 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: Hematopoietic Stem Cell TransplantationExperimental Treatment7 Interventions

All patients will receive a CD3+/CD19+ depleted stem cell transplant. In this study, the investigators will use HLA mismatched unrelated or haploidentical related donor peripheral blood stem cells. Prior to transplantation, the marrow (90-95%) will be negatively selected for CD3/CD19 using the ClinicMACs® depletion device. The remaining (5-10%) will undergo CD45+RA+ depletion and be frozen for future use as an immune boost. Subjects will undergo hematopoietic stem cell transplant utilizing CD3+/CD19+ depleted cells following conditioning therapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alemtuzumab

2004

Completed Phase 4

~1880

Fludarabine

2012

Completed Phase 4

~1860

Thiotepa

2008

Completed Phase 3

~2120

Hydroxyurea

2006

Completed Phase 4

~3490

Rituximab

1999

Completed Phase 4

~2990

0 / 7Eligibility 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 Anemia include hydroxyurea, blood transfusions, and stem cell transplantation. Hydroxyurea works by increasing fetal hemoglobin production, which reduces the formation of sickle-shaped red blood cells and decreases the frequency of painful crises and other complications. Blood transfusions help by increasing the number of normal red blood cells, thereby improving oxygen delivery and reducing the risk of stroke. Stem cell transplantation, particularly using mismatched unrelated or haploidentical related donors with T-cell depletion, aims to replace the patient's defective bone marrow with healthy stem cells, potentially curing the disease. T-cell depletion is crucial as it reduces the risk of graft-versus-host disease, a common and serious complication in mismatched transplants. These treatments are vital as they address the underlying issues of Sickle Cell Anemia, improving quality of life and reducing morbidity and mortality.

Hematopoietic stem cell transplantation for people with sickle cell disease.The prevention and management of stroke in sickle cell anaemia.Collaborative multicenter investigation of marrow transplantation for sickle cell disease: current results and future directions.