Sickle Cell DiseasePhase 1/2RUX-HAPLONCT07252050
Ruxolitinib-Enhanced Haplo HCT for Children and Young Adults With Sickle Cell Disease
A Phase 1/2 study testing Ruxolitinib in people with Sickle Cell Disease and Hematopoetic Stem Cell Transplant, run by Arkansas Children's Hospital Research Institute at 4 sites in United States.
Trial summary
This trial will determine whether adding ruxolitinib to a reduced intensity conditioning (RIC) regimen reduces the rate of graft failure following haploidentical (haplo) hematopoietic cell transplant (HCT) for children and young adults with sickle cell disease (SCD). Read more about this study
- Who is it for?
- Ages 12 to 45 years
- Conditions the study is for
- Sickle Cell Disease, Hematopoetic Stem Cell Transplant, Haploidentical Hematopoietic Stem Cell Transplant
- What is being tested?
- Ruxolitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 4 sitesUnited States
- Study dates
- 8 Jun 2026to 19 Nov 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants with any genotypic form of SCD aged 12 - 45 years at enrollment with ≥1 of the following:
- History of stroke and/or vasculopathy, including evidence of asymptomatic cerebrovascular disease for pediatric patients.
- Recurrent moderate-severe acute chest syndrome (ACS)
- Recurrent vaso-occlusive pain episodes requiring parenteral analgesia despite the institution of supportive care.
- Need for chronic transfusion therapy to prevent vaso-occlusive complications (i.e. pain, stroke, and ACS).
- For adult patients, an echocardiographic finding of tricuspid valve regurgitant jet velocity (TRJV) ≥ 2.7 m/sec.
- Participants must have an HLA haploidentical first degree relative (parent, sibling, or half sibling) who is willing and able to donate bone marrow.
- Participants must meet institutional eligibility criteria for HCT.
Who cannot join
- Presence of an HLA-matched sibling who is willing and able to donate bone marrow.
- Uncontrolled infection, evidence of active TB, Hepatitis B or C infection, or HIV seropositivity or infection.
- Previous HCT or solid organ transplant.
- CNS revascularization procedure, myocardial infarction, pulmonary embolus or deep vein thrombosis in the past 6 months.
- Use of medications which significantly interfere with ruxolitinib metabolism.
- Known hypersensitivity or severe reaction to ruxolitinib or any component of the conditioning regimen or its excipients.
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- Inability to swallow and retain oral medication (use of nasogastric or gastrostomy tube permitted).
- History of malignancy except resected basal cell carcinoma or treated carcinoma in-situ.
- Participation in another clinical trial involving an investigational or off-label use of a drug or device in the past 3 months.
- Currently pregnant or breast feeding.
- Clinically significant, uncontrolled autoimmune disease.
- High-titer anti-donor specific HLA antibodies (without review and approval by Study Chair).
- Participant (or guardian) inability or unwillingness to comply with the dose schedule and study evaluations, comprehend or sign informed consent and utilize a highly effective method of contraception (for participants of child-bearing potential).
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, pose a significant risk to the subject, or interfere with interpretation of study data.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Children's Healthcare of Atlanta
Atlanta, Georgia, 30329
Julia Gliwinski, (404) 785-5532, BMT@choa.org
Elizabeth Stenger, MD
- Not yet recruiting
Children's Hospital of Colorado
Aurora, Colorado, 80045
Chris McKinney, MD
- Not yet recruiting
Manning Family Children's
New Orleans, Louisiana, 70118
Wyvonnia Walker, 504-988-9378, wwalker6@tulane.edu
Maria Pereda Ginocchio, MD
- Not yet recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Nykirah Turner, hatchettn@chop.edu
Timothy Olson, MD, PhD
About this study
Official title: Ruxolitinib-Enhanced Conditioning for Pediatric and Young Adult Patients With Symptomatic Sickle Cell Disease Undergoing Haploidentical Hematopoietic Cell Transplantation
This trial will determine whether adding ruxolitinib to a reduced intensity conditioning (RIC) regimen reduces the rate of graft failure following haploidentical (haplo) hematopoietic cell transplant (HCT) for children and young adults with sickle cell disease (SCD).
This study will enroll and treat up to 24 participants. Recruitment is expected to last for about 2 years and participants will be followed for an additional 2 years post-HCT.
Read the detailed description
While haplo HCT following a RIC regimen cures most patients with SCD, graft failure (GF) can occur and result in return of SCD. GF occurs more often in pediatric SCD patients and can be associated with significant morbidity and/or mortality. Development of strategies which reduce the risk of GF is needed to further improve haplo HCT outcomes for SCD, particularly in pediatric patients. This trial hopes to demonstrate that addition of ruxolitinib to a RIC regimen will reduce the incidence of GF without increasing conditioning-related toxicities.
The RUX-HAPLO study is a Phase 1/2 single-arm, multi-center, open-label trial for pediatric and young adult patients undergoing haplo HCT for SCD. The study will enroll up to 24 participants over approximately 2 years. All participants will receive cytoreduction with hydroxyurea (HU) for at least 60 days (Day -70 to Day -10) prior to the start of conditioning. All participants will then receive a RIC regimen consisting of cyclophosphamide, fludarabine, thiotepa, ATG and TBI beginning on Day -9. Ruxolitinib will begin during conditioning and will continue post-HCT. Participants will also receive GVHD prophylaxis with post-transplant cyclophosphamide, in addition to sirolimus or a calcineurin inhibitor.
The primary objective is to estimate 1-year event-free survival (EFS) with primary or secondary GF or death counting as events for this endpoint.
- Conditions
- Sickle Cell Disease, Hematopoetic Stem Cell Transplant, Haploidentical Hematopoietic Stem Cell Transplant, Haploidentical Stem Cell Transplantation, Graft Failure
- Being tested
- Ruxolitinib
- Keywords
- Sickle cell disease, Hematopoietic cell transplant, Ruxolitinib, Pediatric, Young Adult, Haplo
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called Jakafi
All participants will receive ruxolitinib beginning during conditioning in addition to conventional RIC and GVHD prophylaxis.
| Study group | Role | What they receive |
|---|---|---|
| Ruxolitinib-Enhanced RIC | Experimental | Pediatric and young adult participants who are undergoing haplo HCT for SCD will receive RIC with fludarabine, cyclophosphamide, thiotepa, ATG and low-dose TBI along with ruxolitinib. Ruxolitinib will continue post-HCT in addition to post-transplant cyclophosphamide and sirolimus or a calcineurin inhibitor for GVHD prophylaxis. Receives: Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival
Event Free Survival (EFS) is defined as survival without a qualifying event (primary or secondary GF, second HCT or death).
Measured: 1 year post-HCT
Secondary outcomes (15)
Overall Survival
Overall survival will be described at 1 and 2 years post-HCT including death from any cause after HCT.
Measured: 1 and 2 years post-HCT
Event Free Survival
Event Free Survival (EFS) is defined as survival without a qualifying event (primary or secondary GF, second transplant or death).
Measured: 2 years post-HCT
Neutrophil Recovery
The time to neutrophil recovery, in days, will be reported. Neutrophil recovery is defined as the first of 3 measurements on different days when the absolute neutrophil count is ≥500/μL after nadir.
Measured: Up to Day 60 post-HCT
Platelet Recovery
The time to platelet recovery, in days, will be reported. Platelet recovery is defined as the first day the platelet count is ≥50,000/μL of blood, without a transfusion in the preceding 7 days with the exception of a platelet transfusion specifically to achieve a platelet threshold to allow an elective invasive procedure.
Measured: Up to Day 180 post-HCT
Acute GVHD
Incidence of overall and severe (Grade 3-4) acute GVHD (based on MAGIC criteria) will be estimated at until Day 100 post-HCT.
Measured: Up to Day +100 post-HCT
Chronic GVHD
Incidence of overall and severe chronic GVHD (according to the NIH consensus criteria) will be estimated at 6 months, 1 year, 18 months and 2 years post-HCT.
Measured: 6 months to 2 years post-HCT
Donor hematopoietic chimerism
Characterization of donor chimerism in peripheral blood for lymphoid and myeloid fractions will be performed at day 28, 60, 100, and 180 and 1 and 2 years post-HCT.
Measured: Day 28 to 2 years post-HCT
Primary Graft Failure
The incidence of primary graft failure (GF) by day 42 post-HCT will be estimated. Primary GF is defined as never achieving ≥ 5% donor whole blood or myeloid chimerism. Second infusion of stem cells is also considered indicative of primary GF.
Measured: Day 42 post-HCT
Secondary Graft Failure
The incidence of secondary graft failure (GF) by 2 years post-HCT will be estimated. Secondary GF is defined as < 5% donor whole blood or myeloid chimerism beyond day +42 post-HCT in participants with prior documentation of hematopoietic recovery with > 5% donor cells by day +42 post-HCT. Second infusion of stem cells beyond Day +42 is also considered indicative of secondary GF.
Measured: Up to 2 years post-HCT
Hepatic VOD/SOS
The incidence of hepatic veno-occlusive disease (VOD)/sinusoidal obstruction by 2 years post-HCT will be estimated.
Measured: Up to 2 years post-HCT
IPS
The incidence of idiopathic pneumonia syndrome (IPS) by 2 years post-HCT will be estimated.
Measured: Up to 2 years post-HCT
CNS Toxicity
The incidence of CNS toxicity, defined as seizures, intracranial hemorrhage (ICH), posterior reversible encephalopathy syndrome (PRES) or reversible posterior leukoencephalopathy syndrome (RPLS) will be estimated.
Measured: Up to 2 years post-HCT
Significant infections
The incidence of cytomegalovirus (CMV) infection, adenovirus infection, Epstein-Barr Virus (EBV) post-transplant lymphoproliferative disease (PTLD), or other clinically significant viral reactivations, invasive fungal infections and bacterial sepsis will be estimated.
Measured: Up to 2 years post-HCT
Prolonged Immunosuppressive Therapy
The proportion of participants receiving immunosuppressive therapy beyond 1 year post-HCT because of GVHD or concerns about graft rejection will be determined.
Measured: Up to 2 years post-HCT
SCD-related Complications
SCD-related complications at 6 months, 1 and 2 years post-HCT will be described.
Measured: Up to 2 years post-HCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2025
- Study start8 Jun 2026 (estimated)
- Primary completion19 Nov 2028 (estimated)
- Study completion19 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Arkansas Children's Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Healthcare of Atlanta, Emory University, Incyte Corporation
- Responsible party
- Sponsor
- Investigators
- Laura McLaughlin, MD, Principal investigator, Arkansas Children's Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07252050
- Sponsor's protocol ID
- 24-0735
- Acronym
- RUX-HAPLO
- Status last verified
- Jun 2026
- First submitted
- 14 Nov 2025
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No