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

About the study

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.

Study point of contact

Julia M Varga
(301) 402-3595
[email protected]
Courtney D Fitzhugh, M.D.
(301) 402-6496
[email protected]

Locations

1 United States site

Age

> 2 Years

Phase

Phase 1/Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Procedure

participation requirements

-RECIPIENTS:

Patients with any type of sickle cell disease who are at high risk for disease-related cerebrovascular morbidity or early mortality, defined by having severe end-organ damage (A, B, C, D, or E):

A. A neurologic event resulting in focal neurologic deficits that lasted >= 24 hours (classical clinical definition of stroke, not requiring imaging studies of the brain) OR a focal neurological event resulting in abnormalities on T2- weighted or FLAIR images using an MRI scan, indicative of an acute infarct, with no other reasonable medical explanation (definition of a stroke supported with MRI imaging scans of the brain), OR both; OR

B. Tricuspid regurgitant jet velocity (TRV) of >= 2.7 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 acute chest syndrome episode resulting in intensive care admission requiring non- mechanical ventilatory support: simple nasal cannula, face mask that requires oxygen content (venti mask, non-rebreather), continuous positive airway pressure (CPAP), Bilevel positive airway pressure (BiPAP), high flow nasal cannula (HFNC) or invasive mechanical ventilatory support (delivered by endotracheal tube or tracheostomy). E. Silent cerebral infarct defined as an infarct-like lesion based on an MRI signal abnormality at least 3 mm in one dimension and visible in two planes on FLAIR or T2- weighted images (or similar image with 3D imaging) and documented neurological examination performed by a neurologist demonstrating the participant has a normal neurologic or an abnormality on examination that could not be explained by the location of the brain lesion(s). 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%

participation restrictions

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

Available 6/6 HLA-matched sibling donor
ECOG performance status of 3 or more (See Appendix A)
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.
Major anticipated illness or organ failure incompatible with survival from PBSC transplant
Pregnant or breast-feeding
Donor specific anti-HLA antibodies (DSAs) greater than or equal to 2000 Mean Fluorescence Intensity (MFI)
Patients seronegative for EBV who have EBV seropositive donors

Locations

  • Bethesda, Maryland, United States, National Institutes of Health Clinical Center
Last updated 2022-08-26