Ruxolitinib-Enhanced Haplo HCT for Children and Young Adults With Sickle Cell Disease

NCT ID: NCT07252050

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2029-11-19

Brief 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).

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

All participants will receive ruxolitinib beginning during conditioning in addition to conventional RIC and GVHD prophylaxis.

Interventions

Ruxolitinib

All participants will receive ruxolitinib beginning during conditioning in addition to conventional RIC and GVHD prophylaxis.

Intervention Type: DRUG

Other Intervention Names

Jakafi

Eligibility Criteria

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Healthcare of Atlanta

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: collaborator

Incyte Corporation

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Laura McLaughlin

Lead Principal Investigator/Study Chair

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Laura McLaughlin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

Children's Hospital of Colorado

Aurora, Colorado, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Manning Family Children's

New Orleans, Louisiana, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Central Contacts

Laura McLaughlin, MD

Role: CONTACT

Laura.McLaughlin@childrenscolorado.org

720-777-7008

Kayla Ortiz

Role: CONTACT

Kayla.Ortiz@childrenscolorado.org

720-777-4151

Facility Contacts

Maria Frazer

Role: primary

CTC@choa.org

(404) 785-6162

Wyvonnia Walker

Role: primary

wwalker6@tulane.edu

504-988-9378

Other Identifiers

24-0735

Identifier Type: -

Identifier Source: org_study_id