Phase 3
Completed N=329
A Study of Ruxolitinib vs Best Available Therapy (BAT) in Patients With Steroid-refractory Chronic Graft vs. Host Disease (GvHD) After Bone Marrow Transplantation (REACH3)
Graft-versus-host Disease (GVHD)
Source: ClinicalTrials.gov NCT03112603 ↗
Enrolled (actual)
329
Serious AEs
46.8%
Results posted
Apr 2022
Primary outcomePrimary: Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe Steroid Refractory Chronic Graft Versus Host Disease (SR-cGvHD) Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit — 49.7; 25.6 percentage of participants — p=<0.0001
◆ Published Evidence
Highly cited
490citations · ~98 / year
Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease.
Summary
The purpose of this study is to assess the efficacy of ruxolitinib against best available therapy in participants with steroid-refractory chronic graft-versus-host disease (SR cGvHD).
Linked Publications (5)
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Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease.
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FDA Approval Summary: Ruxolitinib for Treatment of Chronic Graft-Versus-Host Disease after Failure of One or Two Lines of Systemic Therapy.
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Ruxolitinib in Patients With Corticosteroid-Refractory or Corticosteroid-Dependent Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of the Phase III REACH3 Study.
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Clinical considerations for ruxolitinib in the treatment of steroid-refractory acute graft-versus-host disease (GVHD) and steroid-refractory or -dependent chronic GVHD: a plain language summary.
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Impact of concomitant azoles on ruxolitinib treatment in patients with GVHD: post hoc analyses of REACH2 and REACH3.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe Steroid Refractory Chronic Graft Versus Host Disease (SR-cGvHD) Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit |
49.7; 25.6 | <0.0001 sig |
| SECONDARY Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score |
24.2; 11.0 | — |
| SECONDARY Rate of Failure-free Survival (FFS) |
NA; 5.7 | <0.0001 sig |
| SECONDARY Rate of FFS at Study Completion |
38.4; 5.7 | — |
| SECONDARY Best Overall Response (BOR) at Cycle 7 Day 1 |
76.4; 60.4 | 0.0011 sig |
| SECONDARY BOR During Cross-over Treatment With Ruxolitinib |
81.4 | — |
| SECONDARY ORR at the End of Cycle 3 |
54.5; 31.1 | <0.0001 sig |
| SECONDARY Duration of Response Through Study Completion |
NA; 6.4 | — |
| SECONDARY Overall Survival (OS) |
NA; NA | 0.2396 |
| SECONDARY Cumulative Incidence of Non-relapse Mortality (NRM) |
5.45; 4.44; 9.13; 6.43; 15.30; 15.12 | — |
| SECONDARY Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose |
12.7; 13.2; 35.0; 33.1; 48.4; 41.1 | — |
| SECONDARY Percentage of Participants Successfully Tapered Off of All Corticosteroids |
2.5; 2.6; 9.6; 5.4; 14.0; 8.5 | — |
| SECONDARY Cumulative Incidence of Malignancy Relapse/Recurrence (MR) |
1.92; 1.31; 3.22; 2.65; 5.18; 6.08 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) |
2.32; -0.22; 0.62; -1.82; 1.98; -1.05 | — |
| SECONDARY Change From Baseline in EQ-5D-5L |
0.03; -0.01; 0.03; -0.04; 0.04; -0.01 | — |
| SECONDARY Number of Participants With Any Treatment-emergent Adverse Event (TEAE) |
165; 148; 70 | — |
| SECONDARY Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses |
167; 215 | — |
| SECONDARY AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses |
636; 945 | — |
| SECONDARY AUCinf of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses |
642 | — |
| SECONDARY CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses |
15.6; 15.2 | — |
| SECONDARY Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses |
54.0; 50.9 | — |
| SECONDARY Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses |
0.833; 1.00 | — |
| SECONDARY t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses |
2.40; 2.32 | — |
| SECONDARY Utilization of Medical Resources |
57.0; 65.8 | — |
Eligibility Criteria
Inclusion Criteria
- Have undergone allogeneic stem cell transplantation (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
- Evident myeloid and platelet engraftment: Absolute neutrophil count (ANC) > 1000/mm^3 and platelet count > 25,000/ mm^3
- Participants with clinically diagnosed moderate to severe cGvHD according to NIH Consensus Criteria prior to randomization:
- Moderate cGvHD: At least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1
- Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3
- Participants currently receiving systemic or topical corticosteroids for the treatment of cGvHD for a duration of 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, OR
- Increase to prednisolone dose to > 0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose
- Participant must accept to be treated with only one of the following BAT options on Cycle 1 Day 1 (additions and changes are allowed during the course of the study, but only with BAT from the following BAT options): extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib
Exclusion Criteria
- Participants who have received 2 or more systemic treatment for cGvHD in addition to corticosteroids ± CNI for cGvHD
- Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment
- Patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed.
- Participants who were treated with prior JAK inhibitors for aGvHD; except when the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks prior to Cycle 1 Day 1
- Failed prior alloSCT within the past 6 months from Cycle 1 Day 1
- Participants with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed
- Steroid refractory cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for preemptive treatment of malignancy recurrence. Participants 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 cGvHD at doses > 1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1
Data sourced from ClinicalTrials.gov (NCT03112603) and the linked publication. 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.