Nonmyeloablative Haploidentical Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease

• Status: Suspended
• Trial end date: 2026-08-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

...

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Alemtuzumab; Cyclophosphamide; Hydroxyurea; Pentostatin; Sirolimus

Criteria

• INCLUSION CRITERIA-RECIPIENTS:

Patients with any type of sickle cell disease who are at high risk for disease-related morbidity or mortality, defined by having severe end-organ damage (A, B, or C) or potentially modifiable complication(s) not ameliorated by hydroxyurea (D):

A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct or hemorrhage on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy; OR

B. Tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.5 m/s at baseline (without vaso-occlusive crisis) and/or pulmonary hypertension; OR

C. Sickle hepatopathy defined as either ferritin >1000 mcg/L and platelet count < 250,000/uL (without vaso-occlusive crisis) OR direct bilirubin > 0.4 mg/dL and platelet count <250,000/uL (without vaso-occlusive crisis)

D. Any one of the below complications:

• Complication-Vaso-occlusive crises; Eligible for HSCT-Recurrent vaso-occlusive pain crises (at least 2 per year for the last 2 years) despite hydroxyurea

• Complication-Acute chest syndrome; Eligible for HSCT-any ACS while on hydroxyurea.

Non-disease specific:

A. Age greater than or equal to 18 years

B. Haploidentical relative donor available

C. Ability to comprehend and willing to sign an informed consent

D. Negative serum beta-HCG

E. Ejection fraction greater than or equal to 35%

F. Glomerular filtration rate >60 mL/min/1.73m^2 by cystatin C-based or iothalamate-based or other equivalent GFR testing

G. Adjusted DLCO greater than or equal to 35%

EXCLUSION CRITERIA RECIPIENT: (any of the following would exclude the subject from participating)

1. Available 6/6 HLA-matched sibling donor

2. ECOG performance status of 3 or more (See Appendix A)

3. 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.

4. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.

5. Major anticipated illness or organ failure incompatible with survival from PBSC transplant

6. Pregnant or breast-feeding

7. Donor specific anti-HLA antibodies (DSAs) greater than or equal to 2000 Mean Fluorescence Intensity (MFI)

8. Patients seronegative for EBV who have EBV seropositive donors

INCLUSION CRITERIA-DONOR:

Haploidentical relative donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood for research. Related donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all related donors, but is not required for a do le that not all related donors will enroll onto this study.

EXCLUSION CRITERIA-DONOR:

None