Phase 2
Completed N=45
Study of Pharmacokinetics, Activity and Safety of Ruxolitinib in Pediatric Patients With Grade II-IV Acute Graft vs. Host Disease
Source: ClinicalTrials.gov NCT03491215 ↗Enrolled (actual)
45
Serious AEs
53.3%
Results posted
Nov 2024
Primary outcomePrimary: Phase I: Measurement of Pharmacokinetic (PK) Parameter, AUClast, in aGvHD and SR-aGvHD Patients — 252; 372; 154; 239 ng*hr/mL
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase I: Measurement of Pharmacokinetic (PK) Parameter, AUClast, in aGvHD and SR-aGvHD Patients |
252; 372; 154; 239; 259 | — |
| PRIMARY Phase I: Measurement of PK Parameter, Cmax, in aGvHD and SR-aGvHD Patients |
66.1; 105; 49.4; 61.2; 66.5 | — |
| PRIMARY Phase I: Measurement of PK Parameter, T1/2, in aGvHD and SR-aGvHD Patients |
1.33; 1.66; 1.50; 1.86; 1.78 | — |
| PRIMARY Phase I: Measurement of PK Parameter, Ctrough, in aGvHD and SR-aGvHD Patients |
9.27; 9.75; 1.71; 6.18; 3.99 | — |
| PRIMARY Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using AUClast |
252; 154; 372; 239; 259 | — |
| PRIMARY Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using Cmax |
66.1; 49.4; 105; 61.2; 66.5 | — |
| PRIMARY Phase I: Age-based Determination of Recommended Phase 2 Dose (RP2D) Using Ctrough |
8.85; 1.71; 10.6; 6.18; 3.99 | — |
| PRIMARY Phase II: Overall Response Rate (ORR) |
83.3; 83.3; 86.7 | — |
| SECONDARY Percentage of All Patients Who Achieved a Complete Response (CR) or Partial Response (PR) (Durable Overall Response Rate (ORR)) |
55.6; 75.0; 73.3 | — |
| SECONDARY Percentage of Patients Who Achieved OR (CR+PR) at Day 14 |
72.2; 66.7; 86.7 | — |
| SECONDARY Area Under the Curve (AUClast) Versus Efficacy: Impact of AUClast on Overall Response Rate (ORR) at Day 28 |
92.9; 90.9; 86.7 | — |
| SECONDARY Area Under the Curve (AUClast) Versus Efficacy: Impact of AUClast on Durable Response Rate (DRR) at Day 56 |
71.4; 81.8; 73.3 | — |
| SECONDARY Area Under the Curve (AUClast) Versus Safety: Impact of AUClast on Bleeding |
21.4; 18.2; 6.7 | — |
| SECONDARY Area Under the Curve (AUClast) Versus Safety: Impact of AUClast on Infection |
64.3; 63.6; 60.0 | — |
| SECONDARY Duration of Response (DOR) |
2.63; 5.41; 20.37 | — |
| SECONDARY Weekly Cumulative Steroid Dose for Each Patient up to Day 56 |
12.6; 14.1; 11.9; 21.9; 26.1; 21.0 | — |
| SECONDARY Overall Survival (OS) Per Kaplan Meier |
100; 100; 93.33; 88.83; 79.72 | — |
| SECONDARY Event-Free Survival (EFS) Per Kaplan-Meier Estimates |
100; 97.78; 91.11; 86.61; 79.77 | — |
| SECONDARY Failure-Free Survival (FFS) |
11.11; 13.33; 26.67; 26.67; 28.97; 28.97 | — |
| SECONDARY Non Relapse Mortality (NRM) |
0.00; 0.00; 4.44; 8.95; 13.50; 13.50 | — |
| SECONDARY Incidence of Malignancy Relapse (MR)/Progression |
0.00; 3.70; 7.41; 7.41; 11.28; 11.28 | — |
| SECONDARY Cumulative Incidence (CI) of cGvHD |
0.00; 2.22; 11.11; 20.07; 24.65; 24.65 | — |
| SECONDARY Graft Failure |
0.0; 0.0; 0.0 | — |
| SECONDARY Questionnaire on Acceptability and Palatability |
0; 0; 1; 0; 0; 3 | — |
| SECONDARY PK Parameter - Maximum Serum Concentration (Cmax) Versus Efficacy |
— | — |
| SECONDARY PK Parameter: Minimum Serum Concentration (Ctrough) Versus Safety |
— | — |
| SECONDARY PK Parameter: Cmax Versus Safety |
— | — |
| SECONDARY PK Parameter: Ctrough Versus Efficacy |
— | — |
| SECONDARY PK Parameter: Profile of Biomarker Concentration Changes Across Different AUC Quantile Groups |
0.00; -22.43; -79.71; -50.72; -59.48; -10.40 | — |
| SECONDARY PK Parameter: Cmax Versus PD Biomarkers |
— | — |
| SECONDARY PK Parameter: Ctrough Versus PD Biomarkers |
— | — |
| SECONDARY Percentage of Patients Who Achieved Best Overall Response (BOR) up to Day 28 |
94.4; 91.7; 93.3 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female patients age ≥28 days and 1,000/µl and platelet count >20,000/µl. (Use of growth factor supplementation and transfusion support is allowed.)
Exclusion Criteria
- Has received the following systemic therapy for aGvHD: a) Treatment-naïve aGvHD patients have received any prior systemic treatment of aGvHD except for a maximum 72h of prior systemic corticosteroid therapy of methylprednisolone or equivalent after the onset of acute GvHD. Patients are allowed to have received prior GvHD prophylaxis which is not counted as systemic treatment (as long as the prophylaxis was started prior to the diagnosis of aGvHD); OR b) SR-aGvHD patients have received two or more prior systemic treatments for aGvHD in addition to corticosteroids
- Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome with both acute and chronic GvHD features (as defined by Jagasia et al 2015).
- Failed prior alloSCT within the past 6 months.
- Presence of relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed, or who may require rapid immune suppression withdrawal of immune suppression as pre-emergent treatment of early malignancy relapse.
- Acute GvHD occurring after non-scheduled donor leukocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Note: Patients who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
- Any corticosteroid therapy for indications other than aGvHD at doses > 1 mg/kg/day methylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of Screening. Routine corticosteroids administered during conditioning or cell infusion is allowed.
- Patients who received JAK inhibitor therapy for any indication after initiation of current alloSCT conditioning.
Other protocol-defined Inclusion/Exclusion may apply.
Data sourced from ClinicalTrials.gov (NCT03491215). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.