Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia in Individuals With Higher Risk of Transplant Failure

About the study

Background:

– Some sickle cell disease or beta-thalassemia can be cured with transplant. Researchers want to test a variation of transplant that uses low dose radiation and a combination of immunosuppressive drugs. They want to know if it helps a body to better accept donor stem cells.

Objectives:

– To see if low dose radiation (300 rads), oral cyclophosphamide, pentostatin, and sirolimus help a body to better accept donor stem cells.

Eligibility:

– People 4 and older with beta-thalassemia or sickle cell disease that can be cured with transplant, and their donors.

Design:

Participants and donors will be screened with medical history, physical exam, blood test, tissue and blood typing, and bone marrow sampling. They will visit a social worker.
Donors:
may receive an intravenous (IV) tube in their groin vein.
will receive a drug injection daily for 5 or 6 days to move the blood stem cells from the bone marrow into general blood circulation.
will undergo apheresis: an IV is put into a vein in each arm. Blood is taken from one arm, a machine removes the white blood cells that contain blood stem cells, and the rest is returned through the other arm.
Participants:
may undergo red cell exchange procedure.
will remain in the hospital for about 30 days.
will receive a large IV line that can stay in their body from transplant through recovery.
will receive a dose of radiation, and transplant related drugs by mouth or IV.
will receive blood stem cells over 8 hours by IV.
will take neuropsychological tests and may complete questionnaires throughout the transplant process.
must stay near NIH for 4 months. They will visit the outpatient clinic weekly.
will have 5 follow-up visits for 3 years after transplant, then annually.

Study point of contact

Matthew M Hsieh, M.D.
(301) 402-7687
matthewhs@mail.nih.gov
Priscilla S Pollack, R.N.
(301) 496-1781
priscilla.pollack@nih.gov

Locations

1 United States site

Age

> 4 Years

Genotypes

Hb SS

Phase

Phase 2

Study type

Interventional

Gender

All

Interventions

Drug

Procedure

participation requirements

– recipients (must fulfill one disease category in 1 and all of 2)

Disease specific

Patients with severe sickle cell disease (not limited to Hb SS, SC, or S beta-thal) at high risk for disease-related morbidity or mortality, defined by having severe end-organ damage (A, B, C, D, or E) or potentially modifiable complication(s) not ameliorated by hydroxyurea or sickle specific therapy (F):

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

–B. Sickle cell-related renal insufficiency defined by a creatinine level greater than or equal to 1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance less than < 50mL/min OR requiring peritoneal or hemodialysis; OR --C. Tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.5 m/s 40, 41 at baseline; OR --D. Recurrent priapism defined as at least 2 episodes of an erection lasting >4 hours involving the corpora cavernosa and corpus spongiosa; OR

–E. Sickle hepatopathy defined as EITHER ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL at baseline

–F. Any one of the below complications:

—Complication/ Eligible for hydroxyurea*/ Eligible for HSCT

—-Vaso-occlusive crises/ At least 3 hospital admissions in the last year/ More than one hospital admission in the last year while on therapeutic dose of hydroxyurea or sickle cell therapy

Acute chest syndrome/ 2 prior ACS/ any ACS while on hydroxyurea
Osetonecrosis of 2 or more joints/ And significantly affecting their quality of life by Karnofsky score 50-60/ And on hydroxyurea where total hemoglobuin increases less than 1 g/dL or fetal hemoglobin increases less than 2.5 times the baseline level

Red cell alloimmunization/ Transfusion dependent/ Total hemoglobin increases less than 1g/dL while on hydroxurea

2. Patients with beta-thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following:

— portal fibrosis by liver biopsy

inadequate chelation history (defined as failure to maintain adequate compliance with chelation with deferoxamine initiated within 18 months of the first transfusion and administered subcutaneously for 8-10 hours at least 5 days each week)
hepatomegaly of greater than 2cm below the costochondral margin

Non-disease specific:

-Age greater than or equal to 4 years

-6/6 HLA matched family donor available

Ability to comprehend and willing to sign an informed consent
Negative beta-HCG, when applicable

participation restrictions

-recipient (any of the following would exclude the subject from participating)

-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.

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

-Pregnant or lactating

Locations

  • Bethesda, Maryland, United States, National Institutes of Health Clinical Center, 20892 [Recruiting]
Last updated 2022-09-23