Stem Cell Transplant for Sickle Cell Disease

Recruiting in Palo Alto (17 mi)

Overseen byCourtney D Fitzhugh, 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?Background: Peripheral blood stem cell transplantation procedures are used for people with sickle cell disease. Researchers want to improve the success and reduce the complications for these procedures. This might allow more people to have a transplant. Objective: To see if a new transplant regime is effective, safe and well tolerated in people with sickle cell disease. Eligibility: Adults at least 18 years old with sickle cell disease and certain complications. A relative who is a half tissue match. Design: Participants will be screened with medical history, physical exam, and blood tests. Recipients will also have: * Heart, lung, and mental health tests * Chest x-rays * Bone marrow taken from the pelvic bone * Eyes and teeth checked Recipients will have a large central line inserted into a vein for up to 6 months. Donors will have their veins tested and have an IV inserted for 1 day or on rare occasions 2 days. Donors will get a drug to activate bone marrow. It will be injected for about 6 days. Donors will have at least 1 five-hour procedure where bone marrow stem cells will be collected. Blood will be taken from a vein in one arm or in rare cases from a groin vein and put through a machine. Some blood will be saved and the rest will be returned. Stem cells will be taken from the saved blood in a lab and frozen until ready to give to the recipient. Recipients will have: * Stems cells collected and frozen * Hygiene lessons * Bone density scans * Low-dose radiation * Drugs for their immune system * Donor cells infused through their central line * Transfusions After about 30 days, recipients will leave the hospital. They must stay near NIH for 3 months after the transplant and have frequent visits. After returning home, they will have 8 visits over 5 years, then be contacted yearly.

Eligibility Criteria

Adults over 18 with sickle cell disease and severe complications like stroke, high blood flow in the lungs, liver issues, serious lung problems or silent strokes on MRI. They need a half-matched relative donor, good heart and kidney function, and can't be pregnant or breastfeeding. People with uncontrolled infections or major illnesses that could interfere with stem cell transplant recovery are excluded.

Inclusion Criteria

My kidney function test shows a filtration rate above 60 mL/min.

My heart pumps blood effectively.

I am 18 years old or older.

+6 more

Exclusion Criteria

Pregnant or breast-feeding

I have a sibling donor who is a perfect match for me.

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

+4 more

Participant Groups

The trial is testing a new bone marrow transplant method using donors who are half tissue matches for adults with severe sickle cell disease. It includes taking stem cells from the donor's blood after drug stimulation, preparing the recipient's body with radiation and immune system drugs before infusing these cells through a central vein line.

2Treatment groups

Experimental Treatment

Group I: Participants with Sickle Cell Disease with Nonmyeloablative Haplo TransplantsExperimental Treatment6 Interventions

Participants will receive pentostatin on days -21, -17, -13, and -9 and oral cyclophosphamide from days -21 to -8. Alemtuzumab to be infused on days -7 to -3, followed by 400 cGy TBI on day -1. Donor-derived peripheral blood stem cells will be given on Day 0 then cyclophosphamide will be given at 50 mg/kg on day +3. Sirolimus loading dose of 5mg PO q4h x three doses at one day after the completion of cyclophosphamide (on day +4) and continued the following day at 5mg PO q24h to maintain trough levels between 5-15 ng/ml.

Group II: Human Leukocyte Antigens (HLA) Haploidentical Related Stem Cell DonorExperimental Treatment1 Intervention

A haploidentical relative donor will receive filgrastim (G-CSF) 10 to 16 µg/kg/d subcutaneously or intravenously for up to 6 days with apheresis collections of peripheral blood hematopoietic progenitor cells (PBPC) after the 5th day (and after the 6th day if required).

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸 Approved in United States as Cytoxan for: