A Phase 1/2 interventional study of Ruxolitinib in Acute Graft Versus Host Disease, sponsored by Novartis Pharmaceuticals. Completed at 19 sites in 8 countries. Open to participants aged 28 Days to 17 Years. Per ClinicalTrials.gov, last updated 2025-05-04.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 1/2, Interventional, and Treatment
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Among 27 studies testing ruxolitinib in Graft vs Host Disease — 13 open to participants now, 16 under way, 2 of them phase 3. ruxolitinib · Graft vs Host Disease.
Among the 27 studies testing ruxolitinib in Graft vs Host Disease, this one is the 18th largest by enrollment, is the only one that started in 2019, is one of 3 in phase 1/2, and was the 7th registered.
804 studies on the registry are indexed under Graft vs Host Disease; 149 are open to participants now.
Browse Graft vs Host Disease studies →13 of the 27 studies testing ruxolitinib in Graft vs Host Disease are open now, in 12 countries. Recruiting first, the newest first:
Memorial Sloan Kettering Cancer Center · Sites in United States
Ages 18+
Ohio State University Comprehensive Cancer Center · Sites in United States
Ages 18+
Memorial Sloan Kettering Cancer Center · Sites in United States
Ages 18+
Bambino Gesù Hospital and Research Institute · Sites in Austria, Czechia, Denmark and 6 more countries
Ages 3 mo–25 yrs
Novartis Pharmaceuticals · Sites in China
Ages 12–100
By country, each count listing its studies:
ruxolitinib: first FDA approval 2011 (JAKAFI), first EMA approval 2012. What it is approved for, and how studies give it, is on its page →
Of the 103 Graft vs Host Disease studies recruiting now, 51 (50%) set no upper age limit and 42 (41%) stop at 75 or younger; 42 take children under 18; 9 take healthy volunteers.
This study: 28 Days to 17 Years · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
27 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 6 · Phase 2 17 · Phase 3 4 · Phase 4 3
First in 2015; this study’s year is marked. 1 started in 2019.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 45 is above the median of 35 across 639 interventional studies indexed under Graft vs Host Disease.
Median enrollment 54 across the 27 interventional studies. Of the 11 that completed or were terminated, 7 (64%) have results posted.
This tab as a report to print or save as PDF → With an account.
9 of 27 have an industry lead sponsor. The 10 most frequent:
This study is registered under Novartis Pharmaceuticals, one of the names counted as Novartis. Under that name alone:
Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
12 studies in Graft vs Host Disease by Novartis: 2 open now, 4 under way, none of them phase 3. Of 8 finished, 7 (88%) have results posted.
Among the 12 studies in Graft vs Host Disease by Novartis, this one is the 9th largest by enrollment of the 10 interventional ones that give a count, is the only one that started in 2019, is the only one in phase 1/2, and was the 7th registered.
Novartis’s Graft vs Host Disease studies by the year they started, since 2012.
6 of the studies testing ruxolitinib in Graft vs Host Disease that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07238712St. Petersburg State Pavlov Medical UniversityOptimization of Post-transplantation Benadamustine and Cyclophosphamide in Patients With High-risk Myeloid Malignancies and a Partially Mismatched Donor | 2026-12-10 |
| NCT06936566John LevineMAGIC Ruxolitinib for aGVHD | 2027-06-01 |
| NCT06008808Washington University School of MedicineRuxolitinib With and Without CTLA-4 Ig Abatacept for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation | 2027-09-08 |
| NCT07796620Peking University People's HospitalSirolimus+Ruxolitinib+Mycophenolate Mofetil for Prophylaxis of aGVHD in Patients Receiving Haplo-HSCT Who Are Intolerant to CNI | 2027-09-30 |
| NCT07356245Ohio State University Comprehensive Cancer CenterRuxolitinib Maintenance Post-Hematopoietic Stem Cell Transplant T-Cell Lymphoma | 2027-10-31 |
Add all 6 to your calendar (.ics) → With an account.
Among the 27 studies testing ruxolitinib in Graft vs Host Disease, from their registry updates:
Among Novartis’s 12 in Graft vs Host Disease:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
The study was an open-label, single-arm, Phase I/II multi-center study to investigate the PK, activity and safety of ruxolitinib added to the patient's immunosuppressive regimen in infants, children, and adolescents ages ≥28 days to \<18 years old with either grade II-IV aGvHD or grade II-IV SR-aGvHD. The trial design included four age groups: Group 1 included patients ≥12y to \<18y, Group 2 included patients ≥6y to \<12y, Group 3 included patients ≥2y to \<6y, and Group 4 included patients ≥28days to \<2y.
This Phase I/II, open-label, uncontrolled, single-arm, multi-center study investigated PK, activity and safety of ruxolitinib when added to the subject's immunosuppressive regimen in infants, children, and adolescents aged ≥ 28 days to \< 18 years with either grade II-IV treatment naive acute GvHD or grade II-IV SR-acute GvHD following allogeneic HSCT.
The trial subjects were grouped by age as follows:
Subjects remained in the designated age group throughout the duration of the study, based on their age at the start of treatment. All subjects in this study were enrolled and treated for 24 weeks (approximately 6 months) or until early discontinuation.
All subjects were followed for an additional 18 months (total duration = 2 years from enrolment). Where the occurrence of acute GvHD flare require re-initiation of treatment or when extended tapering resulted in ruxolitinib not having been discontinued by the end of 24 weeks, subjects could continue to taper ruxolitinib beyond 24 weeks up to a maximum of 48 weeks.
Subjects ≥ 12 y to \< 18 y (Group 1) were treated with 10 mg BID, this dose was the RP2D, and was used to treat all subjects in this age group in Phase II of Study CINC424F12201. All other age groups were treated with the RP2D determined during Phase I of study CINC424F12201.
Therefore, all ≥12 to \<18 year old subjects were automatically enrolled in Phase II. The first 5 subjects treated in Group 1 underwent extensive PK sampling to inform the RP2D determination of the younger age groups in Phase I.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Other protocol-defined Inclusion/Exclusion may apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorized to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorized to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All pediatric participants received ruxolitinib twice a day (BID) for a planned duration of 24 weeks in either tablet, capsule or oral solution (liquid), depending on the group they were in.
Drug: Ruxolitinib
All enrolled pediatric participants received ruxolitinib as a 5 mg tablet (adult and adolescent formulation) or an oral pediatric formulation (administered as oral solution or capsule dispersed in liquid).
Also known as: INC424
Phase I: Measurement of Pharmacokinetic (PK) Parameter, AUClast, in aGvHD and SR-aGvHD Patients
Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 sparse sampling in Group 4. AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast).
Time frame: Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Phase I: Measurement of PK Parameter, Cmax, in aGvHD and SR-aGvHD Patients
Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 and sparse sampling in Group 4. Cmax: The maximum (peak) observed plasma drug concentration
Time frame: Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Phase I: Measurement of PK Parameter, T1/2, in aGvHD and SR-aGvHD Patients
Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 and sparse sampling in Group 4. T1/2: The elimination half-life associated with the terminal slope (Lambda_z ) of a semi logarithmic concentration-time curve
Time frame: Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Phase I: Measurement of PK Parameter, Ctrough, in aGvHD and SR-aGvHD Patients
Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 and sparse sampling in Group 4. Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
Time frame: Day 7 at pre-dose
Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using AUClast
Phase I: Age-based determination of RP2D in Groups 2 and 3 and was based on observed PK parameters in Groups 1-3 * Group 2: age ≥ 6 to \< 12 years * Group 3: age ≥ 2 to \< 6 years AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast).
Time frame: Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using Cmax
Phase I: Age-based determination of RP2D in Groups 2 and 3 and was based on observed PK parameters in Groups 1-3 * Group 2: age ≥ 6 to \< 12 years * Group 3: age ≥ 2 to \< 6 years Cmax: The maximum (peak) observed plasma drug concentration.
Time frame: Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose
Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using Ctrough
Phase I: Age-based determination of RP2D in Groups 2 and 3 and was based on observed PK parameters in Groups 1-3 * Group 2: age ≥ 6 to \< 12 years * Group 3: age ≥ 2 to \< 6 years Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
Time frame: Day 7 at pre-dose
Phase II: Overall Response Rate (ORR)
Phase II: ORR is defined as the percentage of patients demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response was relative to the organ stage at the start of the study treatment. Complete response (CR) is defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapy for any earlier progression, mixed response or non-response of aGvHD. Partial response (PR) is defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapy for an earlier progression, mixed response or non-response of aGvHD.
Time frame: Day 28
Percentage of All Patients Who Achieved a Complete Response (CR) or Partial Response (PR) (Durable Overall Response Rate (ORR))
Durable ORR at Day 56 was defined as the percentage of all subjects who achieved a complete response (CR) or partial response (PR) at Day 28 and maintained a CR or PR at Day 56. Complete-response was defined as a score of 0 for the acute GvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of acute GvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of acute GvHD. Partial response was defined as improvement of 1 stage in 1 or more organs involved with acute GvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response or non-response of acute GvHD.
Time frame: Day 56
Percentage of Patients Who Achieved OR (CR+PR) at Day 14
ORR at Day 14 was defined as the percentage of participants with complete response (CR) or partial response (PR ) at Day 14 according to standard criteria. Complete response (CR) is defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapy for any earlier progression, mixed response or non-response of aGvHD. Partial response (PR) is defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapy for an earlier progression, mixed response or non-response of aGvHD.
Time frame: Day 14
Area Under the Curve (AUClast) Versus Efficacy: Impact of AUClast on Overall Response Rate (ORR) at Day 28
To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with ORR at day 28). ORR is the percentage of patients with a complete response (CR) or partial response (PR) without additional systemic therapies. Given age group did not have a significant effect on the model fit, the comparison is made indirectly through the odds ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence.
Time frame: Day 28
Area Under the Curve (AUClast) Versus Efficacy: Impact of AUClast on Durable Response Rate (DRR) at Day 56
To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with DRR at day 56). Durable ORR at Day 56 was defined as the percentage of all participants who achieved a complete response (CR) or partial response (PR) at Day 28 and maintained a CR or PR at Day 56. Given age group did not have a significant effect on the model fit, the comparison is made indirectly through the odds ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence.
Time frame: Day 56
Area Under the Curve (AUClast) Versus Safety: Impact of AUClast on Bleeding
To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with safety - bleeding). Bleeding was reported as an adverse event and the AE severity grade was assessed according to CTCAE grading. Given age group did not have a significant effect on the model fit, the comparison is made indirectly through the hazard ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence.
Time frame: 24 weeks
Area Under the Curve (AUClast) Versus Safety: Impact of AUClast on Infection
To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with safety - infection). This analysis includes subjects from F12201 (pediatric and adolescent participants) study. Infections were reported as adverse events and the AE severity grade was assessed according to CTCAE grading. Given age group did not have a significant effect on the model fit, the comparison is made indirectly throughs the hazard ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence
Time frame: 24 weeks
Duration of Response (DOR)
Duration of response was defined as the time from first response (PR or CR) until acute GvHD progression, or the date of additional systemic therapy for acute GvHD. Death without prior observation of acute GvHD progression, and onset of chronic GvHD are considered to be competing risks. Duration of response will be censored at the last response assessment prior to or at the analysis cut-off date, if no events/competing risks occurred on or before 4 weeks (28 days) after the last GvHD assessment. The estimated probability of loss of response at 1, 2 and 6 months after participant's first achievement of CR or PR has been reported. Due to the presence of competing risk, the DOR results are being presented in the form of the probability of loss of response at different time points. As planned in the Statistical Analysis Plan (SAP), this outcome measure is provided for all subjects instead of per age groups.
Time frame: Months 1, 2 & 6
Weekly Cumulative Steroid Dose for Each Patient up to Day 56
The weekly cumulative steroid dose was calculated for each subject up to Day 56 and the overall cumulative steroid dose was calculated for each subject at Day 56.
Time frame: up to 56 days (Week 1 - Week 8)
Overall Survival (OS) Per Kaplan Meier
OS is defined as the time from the start of treatment to the date of death due to any cause. If a subject was not known to have died, then OS was censored at the latest date the subject was known to be alive. The estimated survival probability at 1,2,6,12,18 months after start of treatment has been reported. (on or before the cut-off date). As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
Time frame: 1 Month (M), 2 M, 6M, 12M, 18M
Event-Free Survival (EFS) Per Kaplan-Meier Estimates
EFS is defined as the time from start of treatment to the date of hematologic disease relapse/progression, graft failure, or death due to any cause. If a subject was not known to have any event, then EFS was censored at the latest date the subject was known to be alive (on or before the cut-off date).The estimated probability of event free at 1,2,6,12,18 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
Time frame: 1 Month (M), 2 M, 6M, 12M, 18M
Failure-Free Survival (FFS)
Failure-free (FF) survival was defined as the time from start date of treatment to any of the following: hematologic relapse/progression, non-relapse mortality (NRM) or addition of new systemic acute GvHD treatment. The cumulative incidence (CI) of the onset of failure event at 1,2,6,12,18,24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
Time frame: 1 Month (M), 2M, 6M, 12M, 18M, 24M
Non Relapse Mortality (NRM)
NRM is defined as the time from start of treatment to date of death not preceded by hematologic disease relapse/progression. The cumulative incidence (CI) of non-relapse mortality at 1,2,6,12,18,24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
Time frame: Month (M)1, M2, M6, M12, M18, M24
Incidence of Malignancy Relapse (MR)/Progression
MR was defined as the time from start of treatment to hematologic malignancy relapse/progression. Calculated for patients with underlying hematologic malignant disease. The cumulative incidence (CI) of malignancy relapse/progression at 1,2,6,12,18,24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
Time frame: Month (M) 1, M2, M6, M12, M18, M24,
Cumulative Incidence (CI) of cGvHD
cGvHD is defined as the diagnosis of any cGvHD including mild, moderate, severe. Incidence of chronic GvHD was the time from the start of treatment to onset of chronic GvHD. Cumulative incidence of chronic GvHD was estimated, accounting for deaths without prior onset of chronic GvHD and hematologic disease relapse/progression as the competing risks. The cumulative incidence (CI) of cGvHD at 1, 2, 6, 12, 18 and 24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
Time frame: Month (M) 1, M2, M6, M12, M18, M24
Graft Failure
This was assessed by donor cell chimerism, defined as initial whole blood or marrow donor chimerism for those who had ≥5% donor cell chimerism at baseline. If donor cell chimerism declined to \<5% on subsequent measurements, graft failure was declared.
Time frame: 2 years
Questionnaire on Acceptability and Palatability
Responses from the acceptability and palatability of the study drug (only for subjects administered with oral pediatric formulation starting treatment Day 1) were evaluated from a questionnaire completed by subjects, with the help from parents or caregivers as needed at the following visits: Day 1 (after first dose), Week 4 (1 month) ((after either morning or evening dose of that visit date), Week 24 (6 months) (after either morning or evening dose of that visit date). The choices for taste of the medication were, 'Very good', 'good', 'not good or bad', 'Bad', very bad. The choices for aftertaste of the medication were, 'Very good', 'Good', 'Not good or bad' , 'Bad', Very bad'. The choices for the smell of the medication were, 'Not good or bad' or 'Bad'.
Time frame: Day 1, Week 4 (1 month), Week 24 (6 months)
PK Parameter - Maximum Serum Concentration (Cmax) Versus Efficacy
To assess pharmacokinetic/pharmacodynamic relationship (comparison of Cmax with efficacy). Cmax: The maximum (peak) observed plasma drug concentration.
Time frame: 24 weeks
PK Parameter: Minimum Serum Concentration (Ctrough) Versus Safety
To assess pharmacokinetic/pharmacodynamic relationships (comparison of Ctrough with safety). Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
Time frame: 24 weeks
PK Parameter: Cmax Versus Safety
To assess pharmacokinetic/pharmacodynamics relationship (comparison of Cmax with safety). Cmax: The maximum (peak) observed plasma drug concentration.
Time frame: 24 weeks
PK Parameter: Ctrough Versus Efficacy
To assess pharmacokinetic/pharmacodynamics relationship (comparison of Ctrough with efficacy). Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
Time frame: 24 weeks
PK Parameter: Profile of Biomarker Concentration Changes Across Different AUC Quantile Groups
Describe the relationship between AUC and PD biomarkers. Provide profile of biomarker concentration changes across different AUC quantile groups from baseline. This analysis includes subjects from F12201 study. Population was divided by four level of exposure using AUClast Day 1 quartiles. As planned in SAP, this outcome measure is provided for all subjects instead of per age groups.
Time frame: Week 4
PK Parameter: Cmax Versus PD Biomarkers
To assess pharmacokinetic/pharmacodynamic relationship (comparison of Cmax with PD biomarkers). Cmax: The maximum (peak) observed plasma drug concentration.
Time frame: 24 weeks
PK Parameter: Ctrough Versus PD Biomarkers
To assess pharmacokinetic/pharmacodynamics relationship (Ctrough with PD biomarkers). Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
Time frame: 24 weeks
Percentage of Patients Who Achieved Best Overall Response (BOR) up to Day 28
The best overall response (BOR) was defined as percentage of participants with (complete response (CR) or partial response (PR) at any time point and up to and including Day 28 and before the start of additional systemic therapy for acute GvHD (aGvHD).
Time frame: Up to 28 days and before start of additional aGvHD therapy
A total of 45 subjects were enrolled in the study and treated with the confirmed RP2D, of which at least 20% had treatment naïve acute GvHD and at least 40% had SR-acute GvHD. The study was a single arm study with the subjects grouped as follows: Group 1: subjects ≥ 12y to \< 18y, Group 2: subjects ≥ 6y to \< 12y, Group 3: subjects ≥ 2y to \< 6y, Group 4 was to include subjects ≥ 28 days to \< 2y.
| Milestone | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Started | 18 | 12 | 15 | 0 |
| Rux formulation - received tablet | 18 | 10 | 0 | 0 |
| Rux formulation - received capsule | 0 | 2 | 7 | 0 |
| Rux formulation - received oral solution | 0 | 0 | 8 | 0 |
| Completed | 11 | 10 | 14 | 0 |
| Not completed | 7 | 2 | 1 | 0 |
| Withdrew: Death | 6 | 2 | 1 | 0 |
| Withdrew: Physician decision | 1 | 0 | 0 | 0 |
Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 sparse sampling in Group 4. AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast).
| ng*hr/mL | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Liquid | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|---|
| Phase I: Measurement of Pharmacokinetic (PK) Parameter, AUClast, in aGvHD and SR-aGvHD Patients | 252 ± 186.6 | 372 ± 58.6 | 154 ± 58.1 | 239 ± 65.3 | 259 ± 53.6 | — |
Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 and sparse sampling in Group 4. Cmax: The maximum (peak) observed plasma drug concentration
| ng/ML | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Liquid | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|---|
| Phase I: Measurement of PK Parameter, Cmax, in aGvHD and SR-aGvHD Patients | 66.1 ± 169.8 | 105 ± 71.4 | 49.4 ± 45.7 | 61.2 ± 81.1 | 66.5 ± 60.8 | — |
Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 and sparse sampling in Group 4. T1/2: The elimination half-life associated with the terminal slope (Lambda_z ) of a semi logarithmic concentration-time curve
| hour | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Liquid | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|---|
| Phase I: Measurement of PK Parameter, T1/2, in aGvHD and SR-aGvHD Patients | 1.33 ± 31.7 | 1.66 ± 17.5 | 1.50 ± 6.5 | 1.86 ± 29.9 | 1.78 ± 66.3 | — |
Measurement in acute GvHD and SR-acute GvHD subjects used extensive PK sampling in Groups 1-3 and sparse sampling in Group 4. Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
| ng/ml | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Liquid | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|---|
| Phase I: Measurement of PK Parameter, Ctrough, in aGvHD and SR-aGvHD Patients | 9.27 ± 379.4 | 9.75 ± 255.5 | 1.71 ± 1.2 | 6.18 ± 195.8 | 3.99 ± 277.1 | — |
Phase I: Age-based determination of RP2D in Groups 2 and 3 and was based on observed PK parameters in Groups 1-3 * Group 2: age ≥ 6 to \< 12 years * Group 3: age ≥ 2 to \< 6 years AUClast: The AUC from time zero to the last measurable concentration sampling time (Tlast).
| h*ng/mL | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Capsule | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Tablet | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Liquid | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|---|
| Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using AUClast | 252 ± 186.6 | 154 ± 58.1 | 372 ± 58.6 | 239 ± 65.3 | 259 ± 53.6 | — |
Phase I: Age-based determination of RP2D in Groups 2 and 3 and was based on observed PK parameters in Groups 1-3 * Group 2: age ≥ 6 to \< 12 years * Group 3: age ≥ 2 to \< 6 years Cmax: The maximum (peak) observed plasma drug concentration.
| ng/mL | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Capsule | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Tablet | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Liquid | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|---|
| Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using Cmax | 66.1 ± 169.8 | 49.4 ± 45.7 | 105 ± 71.4 | 61.2 ± 81.1 | 66.5 ± 60.8 | — |
Phase I: Age-based determination of RP2D in Groups 2 and 3 and was based on observed PK parameters in Groups 1-3 * Group 2: age ≥ 6 to \< 12 years * Group 3: age ≥ 2 to \< 6 years Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
| ng/ml | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Capsule | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Tablet | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Liquid | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|---|
| Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using Ctrough | 8.85 ± 538.6 | 1.71 ± 1.2 | 10.6 ± 208.1 | 6.18 ± 195.8 | 3.99 ± 277.1 | — |
Phase II: ORR is defined as the percentage of patients demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response was relative to the organ stage at the start of the study treatment. Complete response (CR) is defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapy for any earlier progression, mixed response or non-response of aGvHD. Partial response (PR) is defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapy for an earlier progression, mixed response or non-response of aGvHD.
| Percentage of participants | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Phase II: Overall Response Rate (ORR) | 83.3 (62.3 to 95.3) | 83.3 (56.2 to 97.0) | 86.7 (63.7 to 97.6) | — |
Durable ORR at Day 56 was defined as the percentage of all subjects who achieved a complete response (CR) or partial response (PR) at Day 28 and maintained a CR or PR at Day 56. Complete-response was defined as a score of 0 for the acute GvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of acute GvHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of acute GvHD. Partial response was defined as improvement of 1 stage in 1 or more organs involved with acute GvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response or non-response of acute GvHD.
| Percentage of participants | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Percentage of All Patients Who Achieved a Complete Response (CR) or Partial Response (PR) (Durable Overall Response Rate (ORR)) | 55.6 (34.1 to 75.6) | 75.0 (47.3 to 92.8) | 73.3 (48.9 to 90.3) | — |
ORR at Day 14 was defined as the percentage of participants with complete response (CR) or partial response (PR ) at Day 14 according to standard criteria. Complete response (CR) is defined as a score of 0 for the aGvHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGvHD in all evaluable organs without administration of additional systemic therapy for any earlier progression, mixed response or non-response of aGvHD. Partial response (PR) is defined as improvement of 1 stage in 1 or more organs involved with aGvHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapy for an earlier progression, mixed response or non-response of aGvHD.
| Percentage of participants | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Percentage of Patients Who Achieved OR (CR+PR) at Day 14 | 72.2 (50.2 to 88.4) | 66.7 (39.1 to 87.7) | 86.7 (63.7 to 97.6) | — |
To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with ORR at day 28). ORR is the percentage of patients with a complete response (CR) or partial response (PR) without additional systemic therapies. Given age group did not have a significant effect on the model fit, the comparison is made indirectly through the odds ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence.
| Percentage of participants | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID Tablet | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Area Under the Curve (AUClast) Versus Efficacy: Impact of AUClast on Overall Response Rate (ORR) at Day 28 | 92.9 | 90.9 | 86.7 | — |
To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with DRR at day 56). Durable ORR at Day 56 was defined as the percentage of all participants who achieved a complete response (CR) or partial response (PR) at Day 28 and maintained a CR or PR at Day 56. Given age group did not have a significant effect on the model fit, the comparison is made indirectly through the odds ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence.
| Percentage of participants | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Area Under the Curve (AUClast) Versus Efficacy: Impact of AUClast on Durable Response Rate (DRR) at Day 56 | 71.4 | 81.8 | 73.3 | — |
To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with safety - bleeding). Bleeding was reported as an adverse event and the AE severity grade was assessed according to CTCAE grading. Given age group did not have a significant effect on the model fit, the comparison is made indirectly through the hazard ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence.
| Percentage of participants | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Area Under the Curve (AUClast) Versus Safety: Impact of AUClast on Bleeding | 21.4 | 18.2 | 6.7 | — |
To assess pharmacokinetic/pharmacodynamic relationship (comparison of AUClast with safety - infection). This analysis includes subjects from F12201 (pediatric and adolescent participants) study. Infections were reported as adverse events and the AE severity grade was assessed according to CTCAE grading. Given age group did not have a significant effect on the model fit, the comparison is made indirectly throughs the hazard ratio across exposure levels in each group. A high response rate may prevent model convergence. Results are shown only upon successful convergence
| Percentage of participants | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Area Under the Curve (AUClast) Versus Safety: Impact of AUClast on Infection | 64.3 | 63.6 | 60.0 | — |
Duration of response was defined as the time from first response (PR or CR) until acute GvHD progression, or the date of additional systemic therapy for acute GvHD. Death without prior observation of acute GvHD progression, and onset of chronic GvHD are considered to be competing risks. Duration of response will be censored at the last response assessment prior to or at the analysis cut-off date, if no events/competing risks occurred on or before 4 weeks (28 days) after the last GvHD assessment. The estimated probability of loss of response at 1, 2 and 6 months after participant's first achievement of CR or PR has been reported. Due to the presence of competing risk, the DOR results are being presented in the form of the probability of loss of response at different time points. As planned in the Statistical Analysis Plan (SAP), this outcome measure is provided for all subjects instead of per age groups.
| Prob. of loss of response in percentage | All Subjects (Group 1, Group 2 & Group 3) | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|
| 1 Month | 2.63 (0.20 to 11.98) | — |
| 2 Months | 5.41 (0.95 to 16.13) | — |
| 6 Months | 20.37 (8.74 to 35.40) | — |
The weekly cumulative steroid dose was calculated for each subject up to Day 56 and the overall cumulative steroid dose was calculated for each subject at Day 56.
| mg/kg | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Week 1 | 12.6 ± 6.04 | 14.1 ± 4.60 | 11.9 ± 5.32 | — |
| Week 2 | 21.9 ± 10.79 | 26.1 ± 9.91 | 21.0 ± 8.03 | — |
| Week 3 | 30.1 ± 16.14 | 36.5 ± 17.18 | 29.0 ± 10.20 | — |
| Week 4 | 37.5 ± 21.19 | 46.9 ± 24.91 | 36.8 ± 12.95 | — |
| Week 5 | 42.6 ± 24.05 | 55.2 ± 31.52 | 42.0 ± 14.76 | — |
| Week 6 | 48.9 ± 24.57 | 61.8 ± 35.80 | 48.8 ± 17.68 | — |
| Week 7 | 51.5 ± 28.34 | 60.6 ± 35.75 | 53.7 ± 19.32 | — |
| Week 8 | 61.3 ± 30.29 | 73.6 ± 43.11 | 58.1 ± 20.50 | — |
OS is defined as the time from the start of treatment to the date of death due to any cause. If a subject was not known to have died, then OS was censored at the latest date the subject was known to be alive. The estimated survival probability at 1,2,6,12,18 months after start of treatment has been reported. (on or before the cut-off date). As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
| survival probability in percentage | All Subjects (Group 1, Group 2 & Group 3) | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|
| 1 Month | 100 (100 to 100) | — |
| 2 Months | 100 (100 to 100) | — |
| 6 Months | 93.33 (80.74 to 97.80) | — |
| 12 Months | 88.83 (75.22 to 95.19) | — |
| 18 Months | 79.72 (64.64 to 88.90) | — |
EFS is defined as the time from start of treatment to the date of hematologic disease relapse/progression, graft failure, or death due to any cause. If a subject was not known to have any event, then EFS was censored at the latest date the subject was known to be alive (on or before the cut-off date).The estimated probability of event free at 1,2,6,12,18 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
| prob. to be event free in percentage | All Subjects (Group 1, Group 2 & Group 3) | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|
| 1 Month | 100 (100 to 100) | — |
| 2 Months | 97.78 (88.25 to 99.68) | — |
| 6 Months | 91.11 (78.03 to 96.57) | — |
| 12 Months | 86.61 (72.59 to 93.75) | — |
| 18 Months | 79.77 (64.72 to 88.93) | — |
Failure-free (FF) survival was defined as the time from start date of treatment to any of the following: hematologic relapse/progression, non-relapse mortality (NRM) or addition of new systemic acute GvHD treatment. The cumulative incidence (CI) of the onset of failure event at 1,2,6,12,18,24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
| CI of treatment failure in percentage | All Subjects (Group 1, Group 2, & Group 3) | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|
| 1 Month | 11.11 (4.02 to 22.27) | — |
| 2 Months | 13.33 (5.34 to 25.01) | — |
| 6 Months | 26.67 (14.72 to 40.18) | — |
| 12 Months | 26.67 (14.72 to 40.18) | — |
| 18 Months | 28.97 (16.48 to 42.68) | — |
| 24 Months | 28.97 (16.48 to 42.68) | — |
NRM is defined as the time from start of treatment to date of death not preceded by hematologic disease relapse/progression. The cumulative incidence (CI) of non-relapse mortality at 1,2,6,12,18,24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
| CI of NRM in percentage | All Subjects (Group 1, Group 2 & Group 3) | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|
| 1 Month | 0.00 (NA to NA) | — |
| 2 Months | 0.00 (NA to NA) | — |
| 6 Months | 4.44 (0.79 to 13.47) | — |
| 12 Months | 8.95 (2.81 to 19.58) | — |
| 18 Months | 13.50 (5.40 to 25.31) | — |
| 24 Months | 13.50 (5.40 to 25.31) | — |
MR was defined as the time from start of treatment to hematologic malignancy relapse/progression. Calculated for patients with underlying hematologic malignant disease. The cumulative incidence (CI) of malignancy relapse/progression at 1,2,6,12,18,24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
| CI of MR/progression in percentage | All Subjects (Group 1, Group 2 & Group 3) | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|
| 1 Month | 0.00 (NA to NA) | — |
| 2 Months | 3.70 (0.25 to 16.23) | — |
| 6 Months | 7.41 (1.24 to 21.37) | — |
| 12 Months | 7.41 (1.24 to 21.37) | — |
| 18 Months | 11.28 (2.74 to 26.60) | — |
| 24 Months | 11.28 (2.74 to 26.60) | — |
cGvHD is defined as the diagnosis of any cGvHD including mild, moderate, severe. Incidence of chronic GvHD was the time from the start of treatment to onset of chronic GvHD. Cumulative incidence of chronic GvHD was estimated, accounting for deaths without prior onset of chronic GvHD and hematologic disease relapse/progression as the competing risks. The cumulative incidence (CI) of cGvHD at 1, 2, 6, 12, 18 and 24 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all subjects instead of per age groups.
| CI of chronic GvHD in percentage | All Subjects (Group 1, Group 2 & Group 3) | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|
| 1 Month | 0.00 (NA to NA) | — |
| 2 Months | 2.22 (0.17 to 10.29) | — |
| 6 Months | 11.11 (4.01 to 22.29) | — |
| 12 Months | 20.07 (9.80 to 32.94) | — |
| 18 Months | 24.65 (13.11 to 38.09) | — |
| 24 Months | 24.65 (13.11 to 38.09) | — |
This was assessed by donor cell chimerism, defined as initial whole blood or marrow donor chimerism for those who had ≥5% donor cell chimerism at baseline. If donor cell chimerism declined to \<5% on subsequent measurements, graft failure was declared.
| Participants | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Graft Failure | 0.0 | 0.0 | 0.0 | — |
Responses from the acceptability and palatability of the study drug (only for subjects administered with oral pediatric formulation starting treatment Day 1) were evaluated from a questionnaire completed by subjects, with the help from parents or caregivers as needed at the following visits: Day 1 (after first dose), Week 4 (1 month) ((after either morning or evening dose of that visit date), Week 24 (6 months) (after either morning or evening dose of that visit date). The choices for taste of the medication were, 'Very good', 'good', 'not good or bad', 'Bad', very bad. The choices for aftertaste of the medication were, 'Very good', 'Good', 'Not good or bad' , 'Bad', Very bad'. The choices for the smell of the medication were, 'Not good or bad' or 'Bad'.
| Participants | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Capsule | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID Liquid | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Day 1: Evaluator: Patient | 0 | 0 | 1 | — |
| Day 1: Evaluator: Legal guardian | 0 | 0 | 3 | — |
| Day 1: Evaluator: Parent | 1 | 4 | 2 | — |
| Day 1: Evaluator: Caregiver | 0 | 0 | 1 | — |
| Day 1: Evaluator: Health care professional | 1 | 3 | 1 | — |
| Day 1: Taste of Medicine: Very good | 0 | 0 | 3 | — |
| Day 1: Taste of Medicine: Good | 1 | 0 | 2 | — |
| Day 1: Taste of Medicine: Not good or bad | 1 | 3 | 0 | — |
| Day 1: Taste of Medicine: Bad | 0 | 2 | 0 | — |
| Day 1: Taste of Medicine: Very bad | 0 | 0 | 0 | — |
| Day 1: Taste of Medicine: Unable to answer the question | 0 | 2 | 3 | — |
| Day 1: Aftertaste of Medicine: Very good | 0 | 0 | 1 | — |
| Day 1: Aftertaste of Medicine: Good | 0 | 1 | 1 | — |
| Day 1: Aftertaste of Medicine: Not good or bad | 2 | 3 | 1 | — |
| Day 1: Aftertaste of Medicine: Bad | 0 | 2 | 0 | — |
| Day 1: Aftertaste of Medicine: Very bad | 0 | 0 | 1 | — |
| Day 1: Aftertaste of Medicine: Unable to answer the question | 0 | 1 | 4 | — |
| Day 1: Smell of Medicine: Very good | 0 | 0 | 1 | — |
| Day 1: Smell of Medicine: Good | 0 | 0 | 1 | — |
| Day 1: Smell of Medicine: Not good or bad | 2 | 4 | 3 | — |
| Day 1: Smell of Medicine: Bad | 0 | 1 | 0 | — |
| Day 1: Smell of Medicine: Very bad | 0 | 0 | 0 | — |
| Day 1: Smell of Medicine: Unable to answer the question | 0 | 2 | 3 | — |
| Week 4: Evaluatohr: Legal guardian | 0 | 1 | 2 | — |
| Week 4: Evaluator: Parent | 1 | 5 | 4 | — |
| Week 4: Evaluator: Health care professional | 1 | 0 | 2 | — |
| Week 4: Taste of Medicine: Very good | 0 | 0 | 0 | — |
| Week 4: Taste of Medicine: Good | 2 | 1 | 4 | — |
| Week 4: Taste of Medicine: Not good or bad | 0 | 4 | 1 | — |
| Week 4: Taste of Medicine: Bad | 0 | 0 | 0 | — |
| Week 4: Taste of Medicine: Very bad | 0 | 1 | 0 | — |
| Week 4: Taste of Medicine: Unable to answer the question | 0 | 0 | 3 | — |
| Week 4: Aftertaste of Medicine: Very good | 0 | 0 | 0 | — |
| Week 4: Aftertaste of Medicine: Good | 0 | 1 | 2 | — |
| Week 4: Aftertaste of Medicine: Not good or bad | 2 | 3 | 1 | — |
| Week 4: Aftertaste of Medicine: Bad | 0 | 1 | 0 | — |
| Week 4: Aftertaste of Medicine: Very bad | 0 | 0 | 0 | — |
| Week 4: Aftertaste of Medicine: Unable to answer the question | 0 | 1 | 5 | — |
| Week 4: Smell of Medicine: Very good | 0 | 0 | 1 | — |
| Week 4: Smell of Medicine: Good | 0 | 0 | 0 | — |
| Week 4: Smell of Medicine: Not good or bad | 2 | 5 | 3 | — |
| Week 4: Smell of Medicine: Bad | 0 | 0 | 1 | — |
| Week 4: Smell of Medicine: Very bad | 0 | 0 | 0 | — |
| Week 4: Smell of Medicine: Unable to answer the question | 0 | 1 | 3 | — |
| Week 24: Evaluator: Patient | — | 1 | 1 | — |
| Week 24: Evaluator: Parent | — | 1 | 0 | — |
| Week 24: Evaluator: Health care professional | — | 0 | 1 | — |
| Week 24: Taste of Medicine: Very good | — | 0 | 2 | — |
| Week 24: Taste of Medicine: Good | — | 1 | 0 | — |
| Week 24: Taste of Medicine: Not good or bad | — | 1 | 0 | — |
| Week 24: Taste of Medicine: Bad | — | 0 | 0 | — |
| Week 24: Taste of Medicine: Very bad | — | 0 | 0 | — |
| Week 24: Taste of Medicine: Unable to answer the question | — | 0 | 0 | — |
| Week 24: Aftertaste of Medicine: Very good | — | 0 | 1 | — |
| Week 24: Aftertaste of Medicine: Not good or bad | — | 2 | 0 | — |
| Week 24: Aftertaste of Medicine: Unable to answer the question | — | 0 | 1 | — |
| Week 24: Smell of Medicine: Very good | — | 0 | 1 | — |
| Week 24: Smell of Medicine: Good | — | 0 | 1 | — |
| Week 24: Smell of Medicine: Not good or bad | — | 2 | 0 | — |
| Week 24: Smell of Medicine: Bad | — | 0 | 0 | — |
| Week 24: Smell of Medicine: Very bad | — | 0 | 0 | — |
| Week 24: Smell of Medicine: Unable to answer the question | — | 0 | 0 | — |
To assess pharmacokinetic/pharmacodynamic relationship (comparison of Cmax with efficacy). Cmax: The maximum (peak) observed plasma drug concentration.
No measurements were reported for this outcome.
To assess pharmacokinetic/pharmacodynamic relationships (comparison of Ctrough with safety). Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
No measurements were reported for this outcome.
To assess pharmacokinetic/pharmacodynamics relationship (comparison of Cmax with safety). Cmax: The maximum (peak) observed plasma drug concentration.
No measurements were reported for this outcome.
To assess pharmacokinetic/pharmacodynamics relationship (comparison of Ctrough with efficacy). Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
No measurements were reported for this outcome.
Describe the relationship between AUC and PD biomarkers. Provide profile of biomarker concentration changes across different AUC quantile groups from baseline. This analysis includes subjects from F12201 study. Population was divided by four level of exposure using AUClast Day 1 quartiles. As planned in SAP, this outcome measure is provided for all subjects instead of per age groups.
| Week 4 percentage change from baseline | AUClast Day 1: 1st Quartile | AUClast Day 1: 2nd Quartile | AUClast Day 1: 3rd Quartile | AUClast Day 1: 4th Quartile | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|
| Biomarker: IL10 | 0.00 (-85.64 to 225.33) | -22.43 (-76.22 to 0.00) | -79.71 (-89.63 to -47.49) | -50.72 (-58.01 to 73.55) | — |
| Biomarker: IL6 | -59.48 (-69.78 to 0.00) | -10.40 (-80.48 to 0.00) | 0.00 (-67.78 to 0.00) | 181.48 (0.00 to 376.54) | — |
| Biomarker: IL8 | -63.63 (-70.48 to -21.03) | 42.57 (-22.15 to 201.65) | 31.79 (-48.56 to 329.67) | 60.02 (-41.74 to 280.49) | — |
| Biomarker: TNFA | -61.45 (-74.05 to -56.96) | 0.00 (-31.03 to 33.67) | -35.34 (-65.90 to -1.41) | 21.49 (-48.52 to 311.76) | — |
| Biomarker: CD4 Assay (CD4 T cells) (%), | -40.49 (-42.67 to -35.51) | 98.07 (16.40 to 206.34) | -3.07 (-17.66 to 115.79) | -42.67 (-62.47 to 92.71) | — |
| Biomarker: CD8 Assay (CD8 T cells) (%), | -51.80 (-69.95 to -20.07) | 64.71 (6.18 to 118.32) | 104.17 (-34.38 to 270.84) | 33.77 (-76.27 to 114.61) | — |
| Biomarker: FOXP3 Assay (Treg cells) (%) | 115.79 (-26.03 to 124.24) | 43.15 (2.08 to 52.17) | 57.14 (-16.49 to 79.73) | -11.11 (-60.56 to 119.05) | — |
| Biomarker: IL14A Assay (Th17 cells) (%) | 5.33 (-33.75 to 10.78) | 140.91 (-25.53 to 570.83) | -7.69 (-18.92 to 131.25) | 38.73 (-57.47 to 203.45) | — |
| Biomarker: LRP5 Assay (B cells) (%), | -15.00 (-30.00 to 122.78) | 25.78 (-42.86 to 300.00) | 140.00 (37.80 to 142.86) | 105.26 (-30.77 to 650.00) | — |
| MVD Assay (NK cells) (%) | -23.82 (-24.21 to 65.52) | 61.81 (34.74 to 98.53) | 22.54 (-18.99 to 69.08) | -0.71 (-34.19 to 72.62) | — |
To assess pharmacokinetic/pharmacodynamic relationship (comparison of Cmax with PD biomarkers). Cmax: The maximum (peak) observed plasma drug concentration.
No measurements were reported for this outcome.
To assess pharmacokinetic/pharmacodynamics relationship (Ctrough with PD biomarkers). Ctrough: The minimum observed plasma concentration at the end of an administration interval (corresponding to the pre-dose concentration prior to the following administration).
No measurements were reported for this outcome.
The best overall response (BOR) was defined as percentage of participants with (complete response (CR) or partial response (PR) at any time point and up to and including Day 28 and before the start of additional systemic therapy for acute GvHD (aGvHD).
| Percentage of participants | Group 1: ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Percentage of Patients Who Achieved Best Overall Response (BOR) up to Day 28 | 94.4 (76.2 to 99.7) | 91.7 (66.1 to 99.6) | 93.3 (72.1 to 99.7) | — |
Adverse events and on-treatment deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, for a maximum duration of 380 days. Post-treatment survival follow-up deaths were collected 31 days after last dose of study medication until the end of the study, up to approx. 23 months.
| Participants | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Total deaths | 6 | 2 | 1 | — |
| On-treatment deaths | 0 | 0 | 0 | — |
| Post-treatment deaths | 6 | 2 | 1 | — |
Collected over Adverse events and on-treatment deaths were collected from the first dose of study treatment up to 30 days after last dose of study medication, for a maximum duration of 380 days. Post-treatment survival follow-up deaths were collected 31 days after last dose of study medication until the end of the study, up to approx. 23 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group 1: Subjects >=12y - <18y - RUX 10mg (On-treatment) | 0/18 (0%) | 11/18 (61.1%) | 18/18 (100%) |
| Group 2: Subjects >=6y - <12y - RUX 5mg (On-treatment) | 0/12 (0%) | 7/12 (58.3%) | 12/12 (100%) |
| Group 3: Subjects >=2y - <6y - RUX 4mg/m2 (On-treatment) | 0/15 (0%) | 6/15 (40%) | 15/15 (100%) |
| All Subjects | 0/45 (0%) | 24/45 (53.3%) | 45/45 (100%) |
| Group 1: Subjects ≥ 12y to < 18y - RUX 10mg (Post-treatment Survival Follow-up) | 6/18 (33.3%) | — | — |
| Group 2: Subjects ≥ 6y to < 12y - RUX 5mg (Post-treatment Survival Follow-up) | 2/12 (16.7%) | — | — |
| Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m2 (Post-treatment Survival Follow-up) | 1/15 (6.7%) | — | — |
| Group 4: Subjects >= 28 Days to < 2y | — | — | — |
| Event | Group 1: Subjects >=12y - <18y - RUX 10mg (On-treatment) | Group 2: Subjects >=6y - <12y - RUX 5mg (On-treatment) | Group 3: Subjects >=2y - <6y - RUX 4mg/m2 (On-treatment) | All Subjects | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg (Post-treatment Survival Follow-up) | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg (Post-treatment Survival Follow-up) | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m2 (Post-treatment Survival Follow-up) | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|---|---|---|
| PyrexiaGeneral disorders | 1/18 | 1/12 | 2/15 | 4/45 | — | — | — | — |
| Septic shockInfections and infestations | 2/18 | 0/12 | 0/15 | 2/45 | — | — | — | — |
| Acute kidney injuryRenal and urinary disorders | 2/18 | 0/12 | 0/15 | 2/45 | — | — | — | — |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/18 | 1/12 | 0/15 | 2/45 | — | — | — | — |
| Pericardial effusionCardiac disorders | 0/18 | 1/12 | 0/15 | 1/45 | — | — | — | — |
| Intestinal perforationGastrointestinal disorders | 0/18 | 1/12 | 0/15 | 1/45 | — | — | — | — |
| Pancreatitis acuteGastrointestinal disorders | 0/18 | 1/12 | 0/15 | 1/45 | — | — | — | — |
| Adenovirus infectionInfections and infestations | 0/18 | 1/12 | 0/15 | 1/45 | — | — | — | — |
| Device related infectionInfections and infestations | 0/18 | 1/12 | 0/15 | 1/45 | — | — | — | — |
| SepsisInfections and infestations | 0/18 | 1/12 | 1/15 | 2/45 | — | — | — | — |
| Event | Group 1: Subjects >=12y - <18y - RUX 10mg (On-treatment) | Group 2: Subjects >=6y - <12y - RUX 5mg (On-treatment) | Group 3: Subjects >=2y - <6y - RUX 4mg/m2 (On-treatment) | All Subjects | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg (Post-treatment Survival Follow-up) | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg (Post-treatment Survival Follow-up) | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m2 (Post-treatment Survival Follow-up) | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 6/18 | 5/12 | 9/15 | 20/45 | — | — | — | — |
| Platelet count decreasedInvestigations | 0/18 | 2/12 | 6/15 | 8/45 | — | — | — | — |
| NeutropeniaBlood and lymphatic system disorders | 6/18 | 2/12 | 1/15 | 9/45 | — | — | — | — |
| ThrombocytopeniaBlood and lymphatic system disorders | 6/18 | 0/12 | 2/15 | 8/45 | — | — | — | — |
| Neutrophil count decreasedInvestigations | 5/18 | 2/12 | 5/15 | 12/45 | — | — | — | — |
| White blood cell count decreasedInvestigations | 0/18 | 2/12 | 5/15 | 7/45 | — | — | — | — |
| HypertensionVascular disorders | 2/18 | 2/12 | 5/15 | 9/45 | — | — | — | — |
| Alanine aminotransferase increasedInvestigations | 5/18 | 2/12 | 2/15 | 9/45 | — | — | — | — |
| Cytomegalovirus test positiveInvestigations | 1/18 | 1/12 | 4/15 | 6/45 | — | — | — | — |
| HypoalbuminaemiaMetabolism and nutrition disorders | 2/18 | 3/12 | 0/15 | 5/45 | — | — | — | — |
The Full Analysis Set (FAS) comprised all subjects to whom study treatment was assigned and who received at least one dose of study treatment. No subjects were enrolled in Group 4.
| Age, Continuous(Months) | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y | Total |
|---|---|---|---|---|---|
| Mean | 172.7 ± 18.94 | 86.1 ± 11.08 | 45.5 ± 14.57 | — | 107.2 ± 58.43 |
| Sex: Female, Male(Participants) | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y | Total |
|---|---|---|---|---|---|
| Female | 5 | 7 | 5 | 0 | 17 |
| Male | 13 | 5 | 10 | 0 | 28 |
| Race/Ethnicity, Customized(Participants) | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y | Total |
|---|---|---|---|---|---|
| White | 11 | 5 | 4 | — | 20 |
| Asian | 3 | 3 | 5 | — | 11 |
| Missing -Note: race is not collected in France | 4 | 4 | 6 | — | 14 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Data sharing details ↗ · www.clinicalstudydatarequest.com
Ran from Feb 2019 to primary completion in Mar 2021, 24 months.
Results were first posted in Nov 2024, 3 years 7 months after primary completion.
Of 39 phase 1/2 interventional studies under Graft vs Host Disease, half reached primary completion within 55 months of starting (the median), counting those still running; a quarter within 35 and three quarters within 76. This study's 24 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Ruxolitinib