NCT07599176

Brief Summary

This is a non-ablative (partial) stem cell transplant for patients with severe sickle cell disease or beta-thalassemia requiring red cell transfusions. The intensity of the transplant is slightly increased from our previous transplant regimens. The goal is to aim for higher percentage of donor cells to stably remain in the recipients long term.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
90

participants targeted

Target at P75+ for phase_1

Timeline
111mo left

Started Jun 2026

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 16, 2026

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 20, 2026

Completed
12 days until next milestone

Study Start

First participant enrolled

June 1, 2026

Expected
6.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2032

3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2035

Last Updated

May 20, 2026

Status Verified

May 15, 2026

Enrollment Period

6.1 years

First QC Date

May 16, 2026

Last Update Submit

May 16, 2026

Conditions

Sickle Cell DiseaseBeta-thalassemia

Keywords

Sickle Cell DiseaseBeta-ThalassemiaStem Cell TransplantChimerism

Outcome Measures

Primary Outcomes (1)

  • Donor myeloid chimerism

    percentage of donor myeloid chimerism

    1 year

Secondary Outcomes (3)

  • Donor CD3 chimerism

    1 year

  • Overall survival

    1 year

  • Acute Graft versus Host Disease

    1 year

Study Arms (2)

Matched related donors

OTHER

Donors for patients

Other: Research blood draw

Transplant recipients

EXPERIMENTAL

Patients with symptomatic sickle cell disease or beta-thalassemia

Radiation: Total Body IrradiationDrug: AlemtuzumabDrug: AbataceptOther: Research blood draw

Interventions

Total Body IrradiationRADIATION

Total Body Irradiation 400 cGy

Transplant recipients
AlemtuzumabDRUG

1 mg/kg

Transplant recipients
AbataceptDRUG

10 mg/kg x 6

Transplant recipients
Research blood drawOTHER

About 5 tablespoons of blood will be collected from donors for research purposes.

Matched related donorsTransplant recipients

Eligibility Criteria

Age4 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • RECIPIENT:
  • Participants must fulfill one disease category (1 or 2) and 3
  • Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having an end-organ damage (A, B, C, D, OR E) or complication(s) not ameliorated by sickle cell-specific therapies (F):
  • A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI ORb
  • B. Abnormal trans-cranial Doppler examination (\>=200 cm/s); OR
  • C. 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 examination, or an abnormality on examination that could not be explained by the location of the brain lesion(s); OR
  • D. Sickle cell related renal insufficiency defined by a creatinine level \>=1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance \<60mL/min/1.73m2 for patients \<16 years of age or \<50mL/min for patients \>16 years of age OR requiring peritoneal or hemodialysis; OR
  • Age (Years): \<= 5 / Upper limit of normal serum creatinine (mg/dl): 0.8
  • Age (Years): 5 \< age \<= 10 / Upper limit of normal serum creatinine (mg/dl): 1.0
  • Age (Years): 10 \< age \<= 15 / Upper limit of normal serum creatinine (mg/dl): 1.2
  • Age (Years): \> 15 / Upper limit of normal serum creatinine (mg/dl): 1.3
  • E. Tricuspid regurgitant jet velocity (TRV) of \>=2.5 m/s in patients at least 3 weeks after a vaso-occlusive crisis; OR
  • F. Recurrent severe priapism defined as at least two episodes of an erection lasting \>=4 hours requiring medical intervention (e.g. aspiration, injection of vasoconstrictor, prior penile surgery.); OR
  • G. Sickle hepatopathy defined as EITHER ferritin \>1000mcg/L OR direct bilirubin \>0.4 mg/dL at baseline; OR
  • H. Vaso-occlusive crises: more than 1 hospital admission per year while on a therapeutic dose of sickle cell treatment /medication; OR
  • +16 more criteria

You may not qualify if:

  • RECIPIENT:
  • Karnofsky or Lanksy performance status of \<40
  • Diffusion capacity of carbon monoxide (DLCO) \<35% predicted (corrected for hemoglobin and alveolar volume). This criterion may be omitted in young children (e.g. near age 5) or other individuals who may have difficulty understanding or complying with instructions of testing.
  • Baseline oxygen saturation of \<85% or PaO2 \<70
  • Left ventricular ejection fraction: \<35% estimated by ECHO
  • Transaminases \>5x upper limit of normal for age
  • 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
  • Major anticipated illness or organ failure incompatible with survival from HCT
  • Pregnant or breastfeeding
  • DONOR:
  • Pregnant or breastfeeding
  • Cognitively impaired subjects

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

MeSH Terms

Conditions

Anemia, Sickle Cellbeta-Thalassemia

Interventions

Whole-Body IrradiationAlemtuzumabAbatacept

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesThalassemia

Intervention Hierarchy (Ancestors)

RadiotherapyTherapeuticsInvestigative TechniquesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsImmunoconjugates

Study Officials

  • John F Tisdale, M.D.

    National Heart, Lung, and Blood Institute (NHLBI)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly S Norris, R.N.

CONTACT

(301) 529-7104kelly.norris@nih.gov

John F Tisdale, M.D.

CONTACT

(301) 402-6497johntis@mail.nih.gov

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 16, 2026

First Posted

May 20, 2026

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 30, 2032

Study Completion (Estimated)

June 30, 2035

Last Updated

May 20, 2026

Record last verified: 2026-05-15

Data Sharing

IPD Sharing
Will not share

We are planning to collect and report data as a group.

Locations

US(1)