Ruxolitinib-Enhanced Haplo HCT for Children and Young Adults With Sickle Cell Disease (RUX-HAPLO)

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.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease; Graft Failure; Haploidentical Hematopoietic Stem Cell Transplant; Hematopoetic Stem Cell Transplant; Haploidentical Stem Cell Transplantation
• Intervention / Treatment: Drug: Ruxolitinib

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Laura McLaughlin, MD; Phone Number: 720-777-7008; Email: Laura.McLaughlin@childrenscolorado.org
• Study Contact Backup: Name: Kayla Ortiz; Phone Number: 720-777-4151; Email: Kayla.Ortiz@childrenscolorado.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • Children's Hospital of Colorado
      • Principal Investigator: Laura McLaughlin, MD
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Children's Healthcare of Atlanta
      • Principal Investigator: Elizabeth Stenger, MD
      • Contact: Julia Gliwinski; Phone Number: 404-785-5532; Email: BMT@choa.org
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Not yet recruiting
      • Manning Family Children's
      • Contact: Wyvonnia Walker; Phone Number: 504-988-9378; Email: wwalker6@tulane.edu
      • Principal Investigator: Maria Pereda Ginocchio, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • Children's Hospital of Philadelphia
      • Principal Investigator: Timothy Olson, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants with any genotypic form of SCD aged 12 - 45 years at enrollment with ≥1 of the following:

   1. History of stroke and/or vasculopathy, including evidence of asymptomatic cerebrovascular disease for pediatric patients.
   2. Recurrent moderate-severe acute chest syndrome (ACS)
   3. Recurrent vaso-occlusive pain episodes requiring parenteral analgesia despite the institution of supportive care.
   4. Need for chronic transfusion therapy to prevent vaso-occlusive complications (i.e. pain, stroke, and ACS).
   5. For adult patients, an echocardiographic finding of tricuspid valve regurgitant jet velocity (TRJV) ≥ 2.7 m/sec.
2. Participants must have an HLA haploidentical first degree relative (parent, sibling, or half sibling) who is willing and able to donate bone marrow.
3. Participants must meet institutional eligibility criteria for HCT.

Exclusion Criteria:

1. Presence of an HLA-matched sibling who is willing and able to donate bone marrow.
2. Uncontrolled infection, evidence of active TB, Hepatitis B or C infection, or HIV seropositivity or infection.
3. Previous HCT or solid organ transplant.
4. CNS revascularization procedure, myocardial infarction, pulmonary embolus or deep vein thrombosis in the past 6 months.
5. Use of medications which significantly interfere with ruxolitinib metabolism.
6. Known hypersensitivity or severe reaction to ruxolitinib or any component of the conditioning regimen or its excipients.
7. Inability to swallow and retain oral medication (use of nasogastric or gastrostomy tube permitted).
8. History of malignancy except resected basal cell carcinoma or treated carcinoma in-situ.
9. Participation in another clinical trial involving an investigational or off-label use of a drug or device in the past 3 months.
10. Currently pregnant or breast feeding.
11. Clinically significant, uncontrolled autoimmune disease.
12. High-titer anti-donor specific HLA antibodies (without review and approval by Study Chair).
13. 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).
14. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ruxolitinib-Enhanced RIC; 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.	Drug: Ruxolitinib; All participants will receive ruxolitinib beginning during conditioning in addition to conventional RIC and GVHD prophylaxis.; Other Names: Jakafi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival	Event Free Survival (EFS) is defined as survival without a qualifying event (primary or secondary GF, second HCT or death).	1 year post-HCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival will be described at 1 and 2 years post-HCT including death from any cause after HCT.	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).	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.	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.	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.	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.	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.	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.	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.	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.	Up to 2 years post-HCT
IPS	The incidence of idiopathic pneumonia syndrome (IPS) by 2 years post-HCT will be estimated.	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.	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.	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.	Up to 2 years post-HCT
SCD-related Complications	SCD-related complications at 6 months, 1 and 2 years post-HCT will be described.	Up to 2 years post-HCT

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Emory University; Incyte Corporation; Children's Healthcare of Atlanta
• Investigators: Principal Investigator: Laura McLaughlin, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): November 19, 2028
• Study Completion (Estimated): November 19, 2029

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ruxolitinib; Pediatric; Sickle cell disease; Young Adult; Hematopoietic cell transplant; Haplo
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; ruxolitinib
• Other Study ID Numbers: 24-0735

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes