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Comparing the Therapeutic Effects of Using Ruxolitinib and Steroids Concurrently to Steroids Alone as Initial Treatment In Patients Diagnosed With Chronic Graft-versus-host Disease at a Grade of Moderate or Higher Severity

A Nation-wide, Multi-center, Prospective, Randomized, Parallel-group, Open-label, Investigator Initiated Pilot Study to Evaluate Efficacy and Safety of Systemic Corticosteroid Plus Ruxolitinib as First-line Therapy in Patients With New-onset Moderate to Severe Chronic Graft-versus-host Disease

Status
Recruiting
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT06756061
Acronym
FRONTJAK-001
Enrollment
88
Registered
2025-01-01
Start date
2025-01-15
Completion date
2029-08-31
Last updated
2025-02-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

GVHD - Graft-Versus-Host Disease, Haematopoietic Stem Cell Transplantation, Neoplasms

Keywords

GvHD-Graft-Versus-Host-Disease, ruxolitinib, first-line

Brief summary

Chronic graft-versus-host disease (cGVHD) is a complication that occurs in 30-40% of recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is a major cause of late non-relapse mortality. In cases where the initial treatment response is inadequate, irreversible tissue damage often persists, making it a fatal complication that significantly reduces quality of life even for long-term survivors. Therefore, the success of first-line treatment is crucial, but to date, there are no approved drugs specifically for the first-line treatment of chronic graft-versus-host disease. Besides corticosteroids, which have been used palliatively for over 50 years, there are no proven effective treatments available. Against this background, this study was designed to explore the potential of new treatments as first-line therapy for chronic graft-versus-host disease, where effective treatment options are currently lacking. Initially, the objective response rate will be analyzed at the 48-week mark based on the NIH Consensus Criteria (Lee 2015). Additionally, the study will evaluate the proportion of patients with steroid-resistant or steroid-dependent conditions, the objective response rate(ORR), failure-free survival(FFS), duration of response(DOR), and the proportion of patients who have reduced corticosteroids. Furthermore, the differences in treatment effects between the two groups of patients will be analyzed based on safety endpoints, including adverse events, laboratory tests, physical examinations, and vital signs.

Interventions

DRUGPrednisone + Jakavi(ruxolitinib)

The experimental group will receive ruxolitinib 10 mg orally twice daily (BID) and prednisone (or equivalent) at a dosage of 1 mg/kg/day. Subjects are orally administered with an investigational medicinal product (IMP) according to their designated treatment group for 48 weeks, and the investigator may adjust the dosage of IMPs based on symptoms of the target disease. (However, after the 48-week mark, participants in the ruxolitinib treatment group may continue to receive ruxolitinib for an additional maximum of 2 years, based on the investigator's judgment regarding the need for ongoing treatment. The total duration of ruxolitinib administration will not exceed 3 years.)

DRUGPrednisone

The control group will receive prednisone (or equivalent) at a dosage of 1 mg/kg/day. Subjects are orally administered with an investigational medicinal product (IMP) according to their designated treatment group for 48 weeks, and the investigator may adjust the dosage of IMPs based on symptoms of the target disease.

Sponsors

Novartis
CollaboratorINDUSTRY
Byung-Sik Cho
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No

Inclusion criteria

\[Inclusion Data\] 1. Adult men and women aged 19 or older based on the date of signing on the informed consent form 2. On the screening visit, those who are diagnosed of a moderate to severe chronic graft-versus-host disease according to 2014 NIH consensus criteria -Moderate: At least one of the following conditions: \>1 point for at least three organs \>2 points for at least one organ except the lungs \>1 point for the lungs -Severe: At least one of the following conditions: \>3 points for at least one organ * At least 2 points for the lungs 3. Those who have no history of systemic treatment for chronic graft-versus-host disease and now need systemic corticosteroid treatment 4. Those whose ECOG (Eastern Cooperative Oncology Group) performance status is 0 to 2. 5. Regardless of the donor (matched sibling-family donor, matched unrelated donor, or partially matched family donor), those who have successfully taken same-type stem cell transplantation (alloSCT) from the marrow, peripheral blood stem cell, or cord blood 6. Those who voluntarily agree on participation in this clinical trial \[Exclusion Data\] 1. Those who meet the following criteria in laboratory tests during the screening and randomization visits * Those whose platelet count is less than or equal to 25,000/mm3 without blood transfusion * Those whose absolute neutrophil count is less than or equal to 1,000/mm3 * Those whose total bilirubin \> 3 x ULN for any reason other than chronic graft-versus-host disease 2. Those with gastrointestinal troubles that hinder the intake and absorption of IMPs and concomitant medicines (systemic corticosteroid) (e.g.: signs such as ulcerative disease, unregulated nausea, vomiting, diarrhea, malabsorption, etc. or small intestine removal) 3. Those with a history of graft-versus-host disease treatment * Corticosteroid administration is permitted for chronic graft-versus-host disease treatment within 72 hours before the randomization visit * Except those who had therapeutic or preventive use of systemic corticosteroids and/or systemic immunosuppressants (CNI, MMF) for acute graft-versus-host disease (In case of prednisone administration for maintenance, only 0.5 mg/kg/day or less is permitted) 4. Those to whom the treatment for chronic graft-versus-host disease cannot begin as prednisone ≥ 0.5 mg/kg/day 5. Those whose same-type stem cell transplantation (alloSCT) has been confirmed as engraft-failed within 6 months before the screening visit 6. Those with an experience of ruxolitinib administration for acute graft-versus-host disease treatment (however, the patient may participate on the assumption that the response to the acute graft-versus-host disease treatment reaches the level of complete or partial response and that there is no ruxolitinib administration history within 4 weeks before the randomization visit. In addition, if ruxolitinib administration was for another disease, the patient may participate unless there is no history of ruxolitinib administration within 4 weeks before the randomization visit.) 7. Those who suffer chronic graft-versus-host disease after an unscheduled donor lymphocyte infusion for proactive treatment to prevent the recurrence of a malignant tumor (Participation is allowed if the scheduled lymphocyte infusion is performed as part of the transplantation procedure, not for the prevention of the recurrence of a malignant tumor.) 8. Those found to have the following history in the screening visit: * Relapsed primary malignancy * Those found to involve an unregulated sinusoidal obstruction syndrome * Those with a history of progressive multifocal leukoencephalopathy (PML) * Nephropathy whose creatinine clearance rate is lower than 30 mL/min (Cockroft Gault equation) * Infections that are clinically active and uncontrolled, requiring treatment, including significant bacteria, fungi, viruses, or parasitic infections. (However, if there are no signs of progression at the time of screening due to appropriate treatment, the infection is considered controlled. The progression of infection is defined by hemodynamic instability due to sepsis, new symptoms caused by the infection, worsening physical signs, or radiological findings. A persistent fever without other signs or symptoms is not interpreted as progressive infection.) * Active tuberculosis * HIV-infected individual * Active infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) that the investigator views as significant * Cardiovascular disease that the investigator considers as clinically significant (acute cardiac infarction (within 6 months before randomization), NYHA class III or IV congestive heart failure, unstable angina (within 6 months before randomization), clinically significant symptomatic cardiac arrhythmia (e.g.: continued ventricular tachycardia, clinically significant level 2 or 3 AV blockage with no pacemaker used), unregulated hypertension) 9. Those allergic or sensitive to additives of IMPs and concomitant medicines (systemic corticosteroid) or similar compounds 10. Patients with genetic problems such as galactose intolerance, lapp lactase deficiency, glucose - galactose malabsorption, etc. 11. Those who are administrated with more than 200 mg of Fluconazole per day 12. Those being treated with systemic medicines that may hinder blood coagulation or platelet functions such as aspirin, heparin, and warfarin (However, those whose aspirin administration does not exceed 150 mg/day may participate.) 13. Pregnant or breast-feeding women 14. Those who do not agree on utilizing proper methods of contraception(e.g. a copper intrauterine device (copper loop), an intrauterine device containing hormones, condoms, a vasectomy, tubal surgery, a spermicide, a vagina-inserted contraceptive, a subdermal implant, an injectable contraceptive, a female condom, oral contraceptive, etc.) during the period of this clinical trial(the period of IP administration and at least 30 days after IP administration ends) 15. Those who have participated in another clinical trial within 30 days before the screening visit and have a history of IMP administration/medical equipment application (However, if the investigator views such a previous trial as not affecting this clinical trial's efficacy and safety assessment such as observational study or retrospective study, the subject may participate.) 16. Those whose participation in this clinical trial is viewed as inappropriate in the investigator's opinion.

Design outcomes

Primary

MeasureTime frameDescription
Overall Response Rate(ORR)on 48 weekORR was defined as the proportion of participants in each study arm achieving either a complete response (CR) or partial response (PR) based on chronic GvHD (cGvHD) assessments in accordance with the National Institutes of Health Consensus Criteria. Response scoring was compared against the organ score at the time of randomization. CR was characterized by the complete resolution of all cGvHD-related signs and symptoms across all evaluable organs, without the initiation or addition of new systemic therapies. PR was defined as improvement in at least one organ (e.g., an increase of 1 or more points on a 4- to 7-point scale, or an increase of 2 or more points on a 10- to 12-point scale) with no progression in other organs or sites and without the need for initiation or addition of new systemic therapies. Participants requiring additional systemic therapies for earlier progression, mixed response, or non-response were classified as not achieving response.

Secondary

MeasureTime frameDescription
Ratio of subjects who are found steroid-refractory or steroid-dependenton Weeks 1, 4, 24, 36 and 48All corticosteroid dosages administered to participants, along with any dose adjustments made during the study, were documented to evaluate participants meeting specific criteria.Steroid-refractory chronic GvHD(SR-cGVHD) was defined as either progression of cGVHD while receiving prednisone at a dose of ≥1mg/kg/day for at least 1 week or stable cGVHD while on≥0.5mg/kg/day or ≥1mg/kg every other day(EOD) for at least 1 month.Response criteria were based on the National Institutes of Health Consensus Criteria.Progression was defined as worsening in any organ or site or the need to initiate or add new systemic therapies.Participants who did not meet the criteria for overall response or progression were categorized as stable.Steroid-dependent participants were defined as those for whom at least two corticosteroid tapering attempts, spaced at least 8 weeks apart, had failed, requiring corticosteroid doses\>0.25 mg/kg/day or \>0.5mg/kg/day EOD to prevent recurrence or progression of symptoms.
Overall Response Rate (ORR) based on the NIH Consensus Criteria on Weeks 24 and 36on Weeks 24 and 36ORR was defined as the proportion of participants in each study arm achieving either a complete response (CR) or partial response (PR) based on chronic GvHD (cGvHD) assessments in accordance with the National Institutes of Health Consensus Criteria. Response scoring was compared against the organ score at the time of randomization. CR was characterized by the complete resolution of all cGvHD-related signs and symptoms across all evaluable organs, without the initiation or addition of new systemic therapies. PR was defined as improvement in at least one organ (e.g., an increase of 1 or more points on a 4- to 7-point scale, or an increase of 2 or more points on a 10- to 12-point scale) with no progression in other organs or sites and without the need for initiation or addition of new systemic therapies. Participants requiring additional systemic therapies for earlier progression, mixed response, or non-response were classified as not achieving response.
Failure-free Survival (FFS)for 48 weeksComposite time to event endpoint incorporating the following FFS events: (i) relapse or recurrence of underlying disease or death due to underlying disease, (ii) nonrelapse mortality, or (iii) addition or initiation of another systemic therapy for cGvHD.
Duration of Response (DOR)for 48 weeksDOR was defined as the time from first response until cGvHD progression, death, or the date of change/addition of systemic therapies for cGvHD and as assessed for responders only. Response was based on cGvHD disease assessments (National Institutes of Health consensus criteria). Duration of response was evaluated in participants who achieved a CR or PR at or before Cycle 7 Day 1.
Ratio of subjects whose daily dosage of systemic corticosteroid is reducedcompared to the baseline on Week 48All corticosteroid dosages administered to participants, along with any dose adjustments made during the study, were documented for assessment of participants with any degree of reduction in daily corticosteroid dose.
Time up to the point of stopping systemic immunosuppressant administration (concomitant medicines other than IMPs)for 48 weeksAll systemic immunosuppressant dosages administered to participants, along with any dose adjustments during the study, were documented to assess participants who successfully discontinued all systemic immunosuppressants. Participants who were classified as having completely tapered off immunosuppressants were those who permanently ceased their use as recorded in the dose administration records and did not restart treatment within the same interval. Participants who discontinued immunosuppressants and remained in follow-up were also considered tapered off, with a recorded dose of 0 in subsequent intervals unless they restarted immunosuppressant treatment or withdrew from the main treatment period.
Change in FACT-BMT((Functional Assessment of Cancer Therapy - Bone Marrow Transplantation) scorecompared to the baseline on Week 24, 36 and 48Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The FACT-BMT is a 50-item self-report questionnaire that measures the effect of a therapy on domains including physical, functional, social/family, and emotional well-being, together with additional concerns relevant for bone marrow transplantation participants. The questions were based on a 5-point Likert scale, where 0 corresponds to not at all and 4 corresponds to very much. The higher the final score, the better the quality of life. The FACT-BMT total score ranges from 0 to 148.
Change in EQ-5D-5L(European Quality of Life 5 Dimension) scorecompared to the baseline on Week 24, 36 and 48The EQ-5D-5L is a descriptive classification consisting of five dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort. The five-level version (no problems, slight problems, moderate problems, severe problems, and extreme problems) uses a 5-point Likert scale, with 1 being no problems and 5 being extreme problems.
Ratio of subjects whose daily dosage of systemic corticosteroid is reduced as much as at least 50%compared to the baseline on Week 48All corticosteroid dosages administered to participants, along with any dose adjustments made during the study, were documented to evaluate participants who achieved a ≥ 50% reduction in their daily corticosteroid dose.

Other

MeasureTime frameDescription
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)for 48 weeksAdverse events (AEs) were defined as the onset or worsening of any undesirable signs, symptoms, or medical conditions that occurred after the participant provided signed informed consent. Abnormal laboratory values or test results following informed consent were classified as AEs only if they resulted in clinical signs or symptoms, were deemed clinically significant, required intervention (e.g., treatment for hematologic abnormalities such as transfusion or hematopoietic stem cell support), or necessitated changes in study medication(s). Treatment-emergent adverse events (TEAEs) were defined as AEs that began or worsened during the on-treatment period, which included both the randomized and cross-over phases of the study.

Countries

South Korea

Contacts

Primary ContactByungSik Cho, M.D. & Ph.D.
cbscho@catholic.ac.kr+82-2-2258-6072

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026