Status:
ACTIVE_NOT_RECRUITING
Addition of JSP191 (C-kit Antibody) to Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia
Lead Sponsor:
National Heart, Lung, and Blood Institute (NHLBI)
Conditions:
Sickle Cell Anemia
Beta Thalassemia
Eligibility:
All Genders
4-100 years
Phase:
PHASE1
PHASE2
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 cu...
Detailed Description
Study Description: We propose to add briquilimab, an antibody targeting CD117 (c-Kit), to the 03-H-0170 regimen to improve myeloid chimerism, in patients considered at high risk for complications fro...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA:
- Recipient: patients must fulfill one disease category (criteria 1) and all of criteria 2
- 1\. 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
- 5 \< age \<= 10 1.0
- 10 \< 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
- Acute chest syndrome (ACS) \|\| Any ACS while on sickle cell treatment /medication
- Osteonecrosis of 2 or more joints \|\| And on sickle cell treatment /medication where total hemoglobin increase less than 1 g/dL or fetal hemoglobin increases \<2.5 times the baseline level
- Red cell alloimmunization \|\| Total hemoglobin increase \<1 g/dL while on therapeutic doses of sickle cell treatment /medication
- 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 2 cm below the costochondral margin or by other imaging scans
- 2\. Non disease specific
- Ages \>=4 years (\>=18 years for phase 1 portion of the study)
- 6/6 HLA matched family donor available
- Ability to comprehend and willing to sign an informed consent, assent obtained from minors
- Negative serum or urine beta-HCG, when applicable
- Agree to use birth control throughout the study and 12 months after drug product infusion.
- Female subjects must agree to use a medically acceptable method of birth control such as oral contraceptive, intrauterine device, barrier and spermicide, or implant/injection from start of screening through 12 months after drug product infusion.
- Male subjects must agree to use effective contraception (including condoms) from start of screening through 12 months after drug product infusion.
- 3\. Patients and Capacity to Consent
- Subject provides informed consent prior to initiation of any study procedures.
- Subject understands and agrees to comply with planned study procedures.
- 4\. Donor
- Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10) are intended for this study. Donors age 4 or older and \>=20 kg, eligible to donate hematopoietic stem cells, who are additionally willing to donate blood for research are eligible for this study. 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 eligible donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study.
- EXCLUSION CRITERIA:
- Recipient exclusion criteria:
- 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
- Donor exclusion criteria:
- Pregnant or breastfeeding
- Cognitively impaired subjects
Exclusion
Key Trial Info
Start Date :
May 12 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 31 2027
Estimated Enrollment :
40 Patients enrolled
Trial Details
Trial ID
NCT05357482
Start Date
May 12 2022
End Date
January 31 2027
Last Update
December 19 2025
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892