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

NCT03077542 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 17006917-H-0069
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sickle Cell Disease

Keywords

Peripheral Blood Stem Cells; Host-Donor Chimerism; Graft-Versus-Host Disease; Haploidentical; Donor Apheresis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Have Not Rejected Their Stem Cell Graft and Who Are Without Severe Graft-versus-host Disease Following Stem Cell Transplant

  The percentage of sickle cell participants at 100 days post-transplant who have not rejected their grafts and who are without severe graft-versus-host disease (GVHD). Severe GVHD is defined as grade 3 or higher for acute GVHD and moderate to severe for chronic GVHD according to NIH Consensus Criteria. Stem cell graft rejection is defined as

  100 days post transplant

Secondary Outcomes (10)

• Chimeric Value That is Required to Maintain Graft Survival and Hematologic Normalcy.

  Up to Year 5

• Incidence of Donor Type Hemoglobin Post-transplant in SCD Patients Who Have Not Been Transfused in the Previous 3 Months.

  1 year

• Number of Participants Who Developed Acute GVHD Grades I, II, III, IV

  Day 100

• Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD)

  Up to Year 5

• Number of Participant That Are Disease-free Survival Following Stem Cell Transplant

  Up to Year 5

Study Arms (2)

Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants

EXPERIMENTAL

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.

Procedure: haploidentical stem cell transplant; Drug: Sirolimus; Drug: Alemtuzumab; Drug: Pentostatin; Drug: Cyclophosphamide; Drug: Hydroxyurea

Human Leukocyte Antigens (HLA) Haploidentical Related Stem Cell Donor

OTHER

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).

Drug: Filgrastim

Interventions

haploidentical stem cell transplant PROCEDURE

haploidentical stem cell transplant

Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants

Sirolimus DRUG

conditioning regimen

Also known as: Rapamune

Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants

Alemtuzumab DRUG

conditioning regimen

Also known as: Campth

Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants

Pentostatin DRUG

conditioning regimen

Also known as: Nipent

Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants

Cyclophosphamide DRUG

conditioning regimen

Also known as: Cytoxan

Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants

Hydroxyurea DRUG

conditioning regimen

Also known as: HU, Hydrea, Droxia

Participants with Sickle Cell Disease with Nonmyeloablative Haplo Transplants

Filgrastim DRUG

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).

Also known as: Granulocyte colony-stimulating factor (G-CSF)

Human Leukocyte Antigens (HLA) Haploidentical Related Stem Cell Donor

Eligibility Criteria

• Age: 2 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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
• 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.
• None

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Limerick E, Hsieh M, Queen J, Grecco ML, Varga J, Brooks J, Coles W, Jeffries N, Fitzhugh CD. Nonmyeloablative pentostatin-cyclophosphamide preconditioning improves rates of engraftment in adults undergoing haploidentical HCT for sickle cell disease. PLoS One. 2026 Mar 23;21(3):e0332282. doi: 10.1371/journal.pone.0332282. eCollection 2026.

  PMID: 41871072 DERIVED

• Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.

  PMID: 36240296 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Sickle Cell; Graft vs Host Disease

Interventions

Sirolimus; Alemtuzumab; Pentostatin; Cyclophosphamide; Hydroxyurea; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Urea; Amides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Courtney Fitzhugh, M.D.
• Organization: National Heart, Lung, and Blood Institute at National Institutes of Health

fitzhughc@nhlbi.nih.gov

301.402.6496

Study Officials

• Courtney F Joseph, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 10, 2017
• First Posted: March 13, 2017
• Study Start: April 6, 2017
• Primary Completion: July 27, 2023
• Study Completion (Estimated): August 31, 2026
• Last Updated: April 23, 2026
• Results First Posted: August 7, 2024

Record last verified: 2026-04

Locations

US (1)