Safety and Efficacy of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation (REACH2)
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ClinicalTrials.gov Identifier: NCT02913261 |
Recruitment Status :
Completed
First Posted : September 23, 2016
Last Update Posted : September 2, 2021
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Condition or disease | Intervention/treatment | Phase |
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Corticosteroid Refractory Acute Graft vs Host Disease | Drug: Ruxolitinib Drug: Best Available Therapy (BAT) | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 310 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase III Randomized Open-label Multi-center Study of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation |
Actual Study Start Date : | March 10, 2017 |
Actual Primary Completion Date : | June 24, 2019 |
Actual Study Completion Date : | April 23, 2021 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Ruxolitinib
Ruxolitinib 10 mg Bis In Diem (BID)
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Drug: Ruxolitinib
Tablet for oral use
Other Name: INC424 |
Active Comparator: Best Available Therapy (BAT)
As selected by the investigator
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Drug: Best Available Therapy (BAT)
Best Available Therapy |
- Overall Response Rate (ORR) [ Time Frame: 28 Days ]ORR is defined as the proportion of patients with a best overall response defined as complete response or partial response
- Durable Overall Response Rate [ Time Frame: Day 56 ]Proportion of all patients in each arm who achieve a complete response (CR) or partial response (PR) at Day 28 (primary endpoint) AND maintain a CR or PR at Day 56.
- ORR [ Time Frame: Day 14 ]Proportion of patients who achieved OR (CR+PR) at Day 14
- Duration of response (DOR) [ Time Frame: Up to 24 months ]DOR is the time from first response until acute Graft versus Host Disease (aGvHD) progression or the date of additional systemic therapies for aGvHD.
- Cumulative steroid dose [ Time Frame: 56 Days ]Weekly cumulative steroid dose for each subject up to Day 56 or end of treatment
- Overall Survival (OS) [ Time Frame: Up to 24 months ]OS is defined as the time from the date of randomization to the date of death due to any cause.
- Event-free survival [ Time Frame: Up to 24 months ]Event-free survival, defined as the time from the date of randomization to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.
- Failure-Free survival (FFS) [ Time Frame: Up to 24 months ]FFS is defined as the time from the date of randomization to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment.
- Non Relapse Mortality (NRM) [ Time Frame: Up to 24 months ]NRM is defined as the time from date of randomization to date of death not preceded by hematologic disease relapse/progression
- Malignancy Relapse/Progression (MR) [ Time Frame: Up to 24 months ]MR is defined as the time from date of randomization to hematologic malignancy relapse/progression. Calculated for patients with underlying hematologic malignant disease.
- Incidence of chronic Graft versus Host Disease (cGvHD) [ Time Frame: Up to 24 months ]cGvHD, defined as the diagnosis of any cGvHD including mild, moderate, severe
- Pharmacokinetic (PK) parameter: Plasma concentration at peak (CMax) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]plasma concentration at peak (Cmax)Ruxolitinib after a single dose and at steady state
- Exposure-efficacy relationship of ruxolitinib in corticosteroid refractory aGvHD [ Time Frame: 168 Days ]exposure-efficacy relationship of ruxolitinib in terms of concentration-effect and dose-effect (effect: overall response rate at Day 28 and durable response at Day 56; Overall survival at 6 months)
- Patient Reported Outcomes (PROs): Functional Assesment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) [ Time Frame: Baseline, Up to 30 day follow-up visit ]Change in Functional Assesment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) from baseline
- Patient Reported Outcomes (PROs): EuroQol-5D-5L change [ Time Frame: Baseline, Up to 30 day follow-up visit ]Change in EuroQol-5D-5D from baseline
- Pharmacokinetic (PK) parameter: Area Under the Curve (AUC) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]AUC from time zero to the last measurable concentration sampling time and from time zero to infinity, and Accumulation ratio (Racc). Ruxolitinib after a single dose and at steady state. AUC at end of a dosing interval (AUC tau) at steady state.
- Pharmacokinetic (PK) parameter: total body clearance of ruxolitinib from the plasma after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]total body clearance of ruxolitinib from the plasma after a single dose and at steady state
- Pharmacokinetic (PK) parameter: apparent volume of distribution during terminal phase after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]apparent volume of distribution during terminal phase after a single dose and at steady state
- Best Overall Response (BOR) [ Time Frame: up to day 28 ]Proportion of patients who achieved OR (CR+PR) at any time point up to and including Day 28 and before the start of additional systemic therapy for aGvHD.
- Pharmacokinetic (PK) parameter: Ctough [ Time Frame: 168 Days ]Minimum concentration (Ctough) of ruxolitininb after a single dose and at steady state in corticosteroid refractory acute GVHD patients

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Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Have undergone Allogeneic Stem Cell Transplanttaion (alloSCT) from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non- myeloablative, myeloablative, and reduced intensity conditioning are eligible
- Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening.
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Confirmed diagnosis of steroid refractory aGvHD defined as patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day [or equivalent prednisone dose 2.5 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:
- Progressing based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR
- Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,OR
- Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria:
- Requirement for an increase in the corticosteroid dose to methylprednisolone ≥2 mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day) , OR
- Failure to taper the methylprednisolone dose to <0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum 7 days.
Exclusion Criteria:
- Has received more than one systemic treatment for steroid refractory aGvHD.
- Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Evidence of uncontrolled viral infection including Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Human Herpes Virus-6 (HHV-6), Hepatitis Virus (HBV), or Hepatitis C Virus (HCV) based on assessment by the treating physician.
- Presence of relapsed primary malignancy, or who have been treated for relapse after the alloHSCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.
Other protocol-defined inclusion/exclusion criteria may apply.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02913261

Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT02913261 |
Other Study ID Numbers: |
CINC424C2301 |
First Posted: | September 23, 2016 Key Record Dates |
Last Update Posted: | September 2, 2021 |
Last Verified: | September 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Plan Description: | 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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
GvHD (Graft versus Host Disease) INC424 ruxolitinib best available therapy (BAT) |
corticosteroid-refractory acute graft vs. host disease allogeneic stem cell transplantation steroid refractory acute graft vs. host disease Janus Kinase (JAK) inhibitor |
Graft vs Host Disease Immune System Diseases |