What side effects are associated with this type of intervention?

The most common treatments for Sickle Cell Anemia include hydroxyurea, chronic transfusions, and immunosuppressants like cyclophosphamide. Hydroxyurea can cause bone marrow suppression, gastrointestinal issues, and lower blood cell counts. Chronic transfusions carry risks such as iron overload, alloimmunization, and transfusion reactions. Immunosuppressants like cyclophosphamide can cause nausea, vomiting, hair loss, and increased susceptibility to infections due to immune suppression.

What prior FDA approvals exist?

The FDA has approved several treatments for Sickle Cell Anemia, focusing on reducing complications and managing symptoms. Hydroxyurea is one of the most well-established treatments, shown to reduce the frequency of painful episodes and other complications. While cyclophosphamide is being studied for its potential to prevent rejection of donor cells in bone marrow transplants, it is not specifically approved for Sickle Cell Anemia. Other treatments include L-glutamine oral powder, voxelotor, and crizanlizumab, which target different aspects of the disease pathology. These treatments aim to improve the quality of life and reduce the disease burden for patients with Sickle Cell Anemia.

What other types of research exist?

Promising novel alternatives to Cyclophosphamide for preventing rejection of donor cells in Sickle Cell Anemia patients include the use of immunosuppressive agents such as alemtuzumab and sirolimus. These agents are part of a low-intensity conditioning regimen that has shown potential in reducing toxicity while effectively preventing graft rejection.

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Cell Therapy

Stem Cell Transplant for Sickle Cell Anemia

Phase 1 & 2

Waitlist Available

Led By Courtney D Fitzhugh, M.D.

Research Sponsored by National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria Checklist

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

Must have

Patients with sickle cell disease (HB SS, SC, or SBeta(0)-thal) at high risk for disease-related morbidity or mortality, defined by having severe end-organ damage (A, B, C, or D) or potentially modifiable complication(s) not ameliorated by hydroxyurea (E):

5.3.4 No history of congestive heart failure or unstable angina, and no history of stroke)

Must not have

ECOG performance status of 3 or more

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up year 5

Awards & highlights

Summary

This trial tests a new bone marrow transplant method for adults with sickle cell disease and Beta-thalassemia. It uses stem cells from a half-matched family donor, low-dose radiation, and immunosuppressant drugs, but no chemotherapy. The goal is to reduce complications and improve outcomes for patients who lack fully matched donors.

Who is the study for?

Adults diagnosed with severe congenital anemias like sickle cell disease or Beta-thalassemia, who have a half-matched family donor. Candidates should be at high risk due to organ damage or complications not improved by other treatments. They must understand and consent to the trial, not be pregnant, and meet specific health criteria.

What is being tested?

The trial is testing a bone marrow transplant (BMT) using stem cells from half-matched donors combined with low-intensity radiation and immunosuppressant drugs (Alemtuzumab, Sirolimus, Cyclophosphamide). It aims to cure anemia without full chemotherapy's side effects.

What are the potential side effects?

Possible side effects include reactions to immunosuppressants like increased infection risk, liver issues from cyclophosphamide, infusion-related reactions from Alemtuzumab and Sirolimus, as well as potential damage from low-dose irradiation.

Eligibility Criteria

Inclusion Criteria

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

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I have sickle cell disease with severe complications not improved by hydroxyurea.

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I have never had congestive heart failure, unstable angina, or a stroke.

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I haven't followed my iron removal treatment as prescribed since my first transfusion.

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I have sickle cell-related liver issues with high ferritin or bilirubin and low platelets.

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I've been hospitalized more than once a year despite taking the highest dose of hydroxyurea I can tolerate.

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I have a family member who is a partial genetic match for a donation.

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I have thalassemia with significant iron overload due to issues like liver problems, poor treatment history, or enlarged liver.

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I have had a stroke confirmed by an MRI or need regular transfusions due to artery issues in my brain.

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I have kidney problems due to sickle cell disease.

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I have had episodes of severe pain due to blocked blood flow.

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I am eligible for a stem cell transplant and have been treated with hydroxyurea.

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I am 18 years old or older.

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I understand and am willing to sign the informed consent; if under age, I have parental consent.

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My hemoglobin S level is 50% or higher, or I have beta thalassemia intermedia.

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I have thalassemia with significant iron overload.

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My heart's tricuspid valve has a high blood flow speed.

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My liver extends more than 2cm below my rib cage.

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I have experienced acute chest syndrome.

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I have been taking the highest dose of hydroxyurea I can tolerate for 6 months.

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I've been hospitalized at least 3 times in the past year.

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My donor is a half-matched family member.

Exclusion Criteria

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

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I need help with my daily activities due to my health condition.

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I don't have any ongoing serious infections.

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I do not have any major illnesses or organ failures that would prevent me from surviving a stem cell transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ year 5

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~year 5

This trial's timeline: 3 weeks for screening, Varies for treatment, and year 5 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Patients With Donor Type Hemoglobin

Secondary study objectives

Chimeric Value That is Required to Maintain Graft Survival and Hematologic Normalcy.

Number of Participants Overall Survival

Number of Participants That Experienced a Transplant-related Mortality

+7 more

Trial Design

3Treatment groups

Experimental Treatment

Group I: Cohort 3Experimental Treatment5 Interventions

PBSC transplant with 100 mg/kg post-transplant cyclophosphamide (PT-Cy)

Group II: Cohort 2Experimental Treatment5 Interventions

PBSC transplant with 50 mg/kg post-transplant cyclophosphamide (PT-Cy)

Group III: Cohort 1Experimental Treatment4 Interventions

PBSC transplant with no post-transplant cyclophosphamide (PT-Cy)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alemtuzumab

2004

Completed Phase 4

~1880

PBSC Transplant

2012

Completed Phase 2

~40

Sirolimus

2013

Completed Phase 4

~2750

Cyclophosphamide

2010

Completed Phase 4

~2320

0 / 24Eligibility 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

Hydroxyurea works by increasing fetal hemoglobin (Hb F) production, which reduces the sickling of red blood cells and decreases vaso-occlusive events. Red blood cell transfusions help by diluting the sickle hemoglobin with normal hemoglobin, thereby reducing the risk of complications like stroke and severe anemia. Bone marrow transplantation offers a potential cure by replacing the defective bone marrow with healthy donor cells, but it requires immunosuppressants like cyclophosphamide to prevent rejection of the donor cells. These treatments are crucial for Sickle Cell Anemia patients as they help manage pain, prevent complications, and improve overall survival and quality of life.

Sickle cell disease.Bone marrow transplantation for sickle cell disease: where do we go from here?