Low-Dose Radiation + Immunosuppressants for Sickle Cell Disease

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by John F Tisdale, M.D.

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

People with severe congenital anemias, such as sickle cell anemia and beta-thalassemia, have been cured with bone marrow transplantation (BMT). The procedure, however, is limited to children younger than the age of 16 because the risks are lower for children than for adults. The purpose of this study is to explore the use of a BMT regimen that, instead of chemotherapy, uses a low dose of radiation, combined with two immunosuppressive drugs. This type BMT procedure is described as nonmyeloablative, meaning that it does not destroy the patient s bone marrow. It is hoped that this type of BMT will be safe for patients normally excluded from the procedure because of their age and other reasons. To participate in this study, patients must be between the ages of 18 and 65 and have a sibling who is a well-matched stem-cell donor. Beyond the standard BMT protocol, study participants will undergo additional procedures. The donor will receive G-CSF by injection for five days; then his or her stem cells will be collected and frozen one month prior to BMT. Approximately one month later, the patient will be given two immune-suppressing drugs, Campath 1-H and Sirolimus, as well as a single low dose of total body irradiation and then the cells from the donor will be infused. Prior to their participation in this study, patients will undergo the following evaluations: a physical exam, blood work, breathing tests, heart-function tests, chest and sinus x-rays, and bone-marrow sampling. ...

Eligibility Criteria

This trial is for adults aged 18-65 with severe congenital anemias like sickle cell disease, who have a sibling as a stem-cell donor. Participants must meet specific health criteria such as normal organ function and not be pregnant or lactating. Those with uncontrolled infections or significant heart/lung problems are excluded.

Inclusion Criteria

I am over 18 and have high ferritin or bilirubin levels indicating liver issues.

I need regular blood transfusions.

You must have one of the following diseases:

Exclusion Criteria

Recipient:

Transaminases greater than 5 times the upper limit of normal for age

Baseline oxygen saturation or less than 85% or PaOa2 less than 70

Treatment Details

Interventions

• Alemtuzumab (Immunosuppressive Drug)
• Peripheral blood hematopoietic progenitor cell Apherisis (Procedure)
• Peripheral blood hematopoietic progenitor cell (PBPC) transplant (Procedure)
• Sirolimus (Immunosuppressive Drug)
• Total Body Irradiation (Radiation)

Trial Overview The study tests a bone marrow transplant (BMT) method using low-dose radiation and immunosuppressive drugs Alemtuzumab and Sirolimus, instead of chemotherapy. This nonmyeloablative BMT aims to be safer for patients normally too old for traditional BMT.

Participant Groups

Group I: Participants with Severe Beta-globin Disorders in Allogeneic Peripheral Blood Stem Cell Transplants Experimental Treatment 3 Interventions

Nonmyeloablative transplant regiment, consisting of alemtuzumab (1 mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and infusion of unmanipulated filgrastim mobilized peripheral blood stem cells from human leukocyte antigen-matched siblings.

Group II: Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor Experimental Treatment 1 Intervention

Participants received Filgrastim to mobilize peripheral blood stem cells for apheresis collection. Collected stem cells of donor will then be infused to HLA matched sibling.

Alemtuzumab is already approved in United States, European Union, 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, MD

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI) Lead Sponsor

References