Addition of JSP191 (C-kit Antibody) to Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia

NCT05357482 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10000539000539-H
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Sickle cell disease (SCD) is an inherited disorder of the blood. It can damage a person s organs and cause serious illness and death. A blood stem cell transplant is the only potential cure for SCD. Treatments that improve survival rates are needed. Objective: To find out if a new antibody drug (briquilimab, JSP191) improves the success of a blood stem cell transplant Eligibility: People aged 13 or older who are eligible for a blood stem cell transplant to treat SCD. Healthy family members over age 13 who are matched to transplant recipients are also needed to donate blood. Design: Participants receiving transplants will undergo screening. They will have blood drawn. They will have tests of their breathing and heart function. They may have chest x-rays. A sample of marrow will be collected from a pelvic bone. Participants will remain in the hospital about 30 days for the transplant and recovery. They will have a large intravenous line inserted into the upper arm or chest. The line will remain in place for the entire transplant and recovery period. The line will be used to draw blood as needed. It will also be used to administer the transplant stem cells as well as various drugs and blood transfusions. Participants will also receive some drugs by mouth. Participants must remain within 1 hour of the NIH for 3 months after transplant. During that time, they will visit the clinic up to 2 times a week. Follow-up visits will include tests to evaluate participants mental functions. They will have MRI scans of their brain and heart.

Conditions

Beta Thalassemia; Sickle Cell Anemia

Keywords

Myeloid Chimerism; Lymphoid Cells; Myeloid Cells; Donor Leukocyte Engraftment; Non-Myeloablative Conditioning

Outcome Measures

Primary Outcomes (1)

• percent myeloid (CD14/15) chimerism

  The primary objective is to determine if addition of CD117 antibody (JSP191) would increase proportion of patients with donor myeloid chimerism =98% at 1 year post transplant.

  1 year post transplant

Secondary Outcomes (11)

• Transplant related mortality

  1 and 2 years post transplant

• Rates of graft failure

  1 and 2 years post transplant

• Rate of viral infection and/or reactivation

  day 100

• Alemtuzumab levels

  day 100

• Rate of chronic GVHD

  1 and 2 years post transplant

Study Arms (2)

briquilimab in stem cell transplant recipients for SCD

EXPERIMENTAL

Affected SCD and beta-thal subjects will receive briquilimab

Radiation: TBI; Drug: Hydroxyurea; Biological: briquilimab; Drug: Filgrastim (G-CSF); Drug: Sirolimus; Biological: Alemtuzumab; Drug: Plerixafor

Stem cell Donors of Recipients undergoing stem cell transplant

NO INTERVENTION

Participants donate stem cells for recipient to undergo stem cell transplant

Interventions

briquilimab BIOLOGICAL

briquilimab, anti-CD117 monoclonal antibody at 0.6mg/kg at day -11 prior to infusion of allogeneic HSCs

briquilimab in stem cell transplant recipients for SCD

TBI RADIATION

300 cGy total body irradiation (TBI, day -2)

briquilimab in stem cell transplant recipients for SCD

Hydroxyurea DRUG

Optimized 4-12 weeks prior to planned transplant date

briquilimab in stem cell transplant recipients for SCD

Filgrastim (G-CSF) DRUG

May be used to minimize the days of neutropenia, and may be administered beginning near day 10 post stem cell infusion at 5 mcg/kg (rounding to the nearest vial) at the discretion of investigator.

briquilimab in stem cell transplant recipients for SCD

Sirolimus DRUG

For immune suppression (day -1)

briquilimab in stem cell transplant recipients for SCD

Alemtuzumab BIOLOGICAL

Alemtuzumab 1 mg/kg of alemtuzumab divided over 5 days (-7 through -3),

briquilimab in stem cell transplant recipients for SCD

Plerixafor DRUG

For autologous HSC collection; dose of plerixafor at 240 mcg/kg (capped at 20mg)

briquilimab in stem cell transplant recipients for SCD

Eligibility Criteria

• Age: 4 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipient: patients must fulfill one disease category (criteria 1) and all of criteria 2
• \. 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-SPECIFC THERAPIES (F):
• A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI OR an abnormal trans-cranial Doppler examination (\>=200 cm/s); OR
• B. Sickle cell related renal insufficiency defined by a creatinine level \>=1.5 times the upper limit of normal (see table below) 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) Upper limit of normal serum creatinine (mg/dl)
• \<= 5 0.8
• \< age \<= 10 1.0
• \< age \<= 15 1.2
• \> 15 1.3
• C. Tricuspid regurgitant jet velocity (TRV) of \>=2.5 m/s in patients at least 3 weeks after a vaso-occlusive crisis; OR
• D. Recurrent tricorporal priapism defined as at least two 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; OR
• F. Any one of the below complications:
• Complication \|\| Eligible for HSCT
• Vaso-occlusive crises \|\| More than 1 hospital admission per year while on a therapeutic dose of sickle cell treatment /medication

You may not qualify if:

• ECOG performance status of 3 or more, or Lanksy performance status of \<40 (See Appendix A).
• 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 PBSC transplant.
• Pregnant or breastfeeding
• Pregnant or breastfeeding
• Cognitively impaired subjects

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 Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Sickle Cell; beta-Thalassemia

Interventions

Hydroxyurea; Filgrastim; Granulocyte Colony-Stimulating Factor; Sirolimus; Alemtuzumab; plerixafor

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; Thalassemia

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Macrolides; Lactones; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• John F Tisdale, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 30, 2022
• First Posted: May 3, 2022
• Study Start: May 12, 2022
• Primary Completion: January 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03-10

Locations

US (1)