TriangleNCT03112603 · CITED IN SOURCE DOCUMENTS
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)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2025-08-12
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).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
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
Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score
Rate of Failure-free Survival (FFS)
Rate of FFS at Study Completion
Best Overall Response (BOR) at Cycle 7 Day 1
BOR During Cross-over Treatment With Ruxolitinib
ORR at the End of Cycle 3
Duration of Response Through Study Completion
Overall Survival (OS)
Cumulative Incidence of Non-relapse Mortality (NRM)
Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose
Percentage of Participants Successfully Tapered Off of All Corticosteroids
Cumulative Incidence of Malignancy Relapse/Recurrence (MR)
Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT)
Change From Baseline in EQ-5D-5L
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
AUCinf of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses
Utilization of Medical Resources
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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 \< 12 months prior to Cycle 1 Day 1 (if applicable), and have a confirmed diagnosis of steroid-refractory cGvHD defined per 2014 NIH consensus criteria irrespective of the concomitant use of a calcineurin inhibitor (CNI), as follows: * A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week, OR * Disease persistence without improvement despite continued treatment with prednisone at \> 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
- healthy Volunteers
- false
- minimum Age
- 12 Years
- sex
- ALL
- std Ages
- CHILD
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Ruxolitinib for the treatment period and extension period.
- intervention Names
- Drug: Ruxolitinib
- label
- Ruxolitinib
- type
- EXPERIMENTAL
- description
- Best available therapy for the treatment period and extension period, with optional crossover to ruxolitinib after Cycle 6.
- intervention Names
- Drug: Extracorporeal photopheresis (ECP)
- Drug: Low-dose methotrexate (MTX)
- Drug: Mycophenolate mofetil (MMF)
- Drug: mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus)
- Drug: Infliximab
- Drug: Rituximab
- Drug: Pentostatin
- Drug: Imatinib
- Drug: Ibrutinib
- label
- Best Available Therapy
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Ruxolitinib
- description
- Ruxolitinib twice daily at the protocol-defined starting dose.
- name
- Ruxolitinib
- other Names
- Jakafi, INCB018424
- type
- DRUG
- arm Group Labels
- Best Available Therapy
- description
- Best available therapy (BAT) will be selected by the investigator for each participant. BAT may not include experimental agents (ie, those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements. The BAT in this study will be among the following treatments currently used in this setting (no other types or combinations of BATs are permitted in this study).
- name
- Extracorporeal photopheresis (ECP)
- type
- DRUG
- arm Group Labels
- Best Available Therapy
- description
- Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
- name
- Low-dose methotrexate (MTX)
- type
- DRUG
- arm Group Labels
- Best Available Therapy
- description
- Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
- name
- Mycophenolate mofetil (MMF)
- type
- DRUG
- arm Group Labels
- Best Available Therapy
- description
- Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
- name
- mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus)
- type
- DRUG
- arm Group Labels
- Best Available Therapy
- description
- Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
- name
- Infliximab
- type
- DRUG
- arm Group Labels
- Best Available Therapy
- description
- Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
- name
- Rituximab
- type
- DRUG
- arm Group Labels
- Best Available Therapy
- description
- Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
- name
- Pentostatin
- type
- DRUG
- arm Group Labels
- Best Available Therapy
- description
- Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
- name
- Imatinib
- type
- DRUG
- arm Group Labels
- Best Available Therapy
- description
- Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
- name
- Ibrutinib
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 330
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- ORR was defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on chronic GvHD (cGvHD) disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies.
- measure
- 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
- time Frame
- Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
- secondary Outcomes
- description
- To assess improvement of symptoms based on the total symptom score (TSS); a responder was defined as having achieved a clinically relevant reduction from Baseline of the TSS. The scale consists of 30 items in 7 subscales (skin, eye, mouth, lung, nutrition, energy, and psychological). Participants reported their level of symptom "bother" over the previous month on a 5-point likert scale: not at all, slightly, moderately, quite a bit, or extremely. Subscale scores and the summary score range from 0 to 100, with a higher score indicating worse symptoms.
- measure
- Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score
- time Frame
- Baseline; Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
- description
- Composite 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.
- measure
- Rate of Failure-free Survival (FFS)
- time Frame
- Baseline to when the last participant reached Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
- description
- Composite 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.
- measure
- Rate of FFS at Study Completion
- time Frame
- From Baseline to Last Participant Last Visit (LPLV) (approximately 5 years)
- description
- BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies. This analysis was based on the primary cutoff date (May 2020).
- measure
- Best Overall Response (BOR) at Cycle 7 Day 1
- time Frame
- up to Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
- description
- BOR was defined as the percentage of participants who achieved an overall response (CR+PR) based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD). Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies.
- measure
- BOR During Cross-over Treatment With Ruxolitinib
- time Frame
- from Crossover Cycle 1 Day 1 to any time point up to and including Crossover Cycle 7 Day 1 (each cycle was comprised of 4 weeks)
- description
- ORR was defined as the percentage of participants in each arm demonstrating a CR or PR based on cGvHD disease assessments (National Institutes of Health Consensus Criteria) without the requirement of additional systemic therapies for an earlier progression, mixed response, or non-response. Scoring of response was relative to the organ score at the time of randomization. CR: complete resolution of all signs and symptoms of cGVHD in all evaluable organs without the initiation or addition of new systemic therapy. PR: improvement in at least one organ (e.g., improvement of 1 or more points on a 4- to 7-point scale, or an improvement of 2 or more points on a 10- to 12-point scale) without progression in other organs or sites, initiation, or addition of new systemic therapies.
- measure
- ORR at the End of Cycle 3
- time Frame
- Cycle 4 Day 1 (each cycle was comprised of 4 weeks)
- description
- DOR 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. The analysis included a larger number of participants than the number of participants who achieved CR or PR at Cycle 7 Day 1 (82 ruxolitinib and 42 BAT) because the analysis took into account not only those participants who achieved CR or PR at Cycle 7 Day 1, but also participants who achieved CR or PR before Cycle 7 Day 1 but who may have lost their response at Cycle 7 Day 1. For this reason, the number of participants in this analysis does not align with the best overall response (BOR) at Cycle 7 Day 1. This analysis was based on the cutoff date upon study completion (December 2022).
- measure
- Duration of Response Through Study Completion
- time Frame
- from first response to LPLV (approximately 5 years)
- description
- Overall survival was defined as the time from the date of randomization to the date of death due to any cause.
- measure
- Overall Survival (OS)
- time Frame
- from the date of randomization to the date of death due to any cause up to LPLV (approximately 5 years)
- description
- Defined as the cumulative incidence rate from competing risk analysis for NRM from the date of randomization to the date of death not preceded by underlying disease relapse/recurrence.
- measure
- Cumulative Incidence of Non-relapse Mortality (NRM)
- time Frame
- Months 3, 6, 12, 18, 24, 30, and 36
- description
- All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants with a ≥ 50% reduction in daily corticosteroid dose.
- measure
- Percentage of Participants With a ≥ 50% Reduction in Daily Corticosteroid Dose
- time Frame
- from Day 15 up to Day 182
- description
- All corticosteroid dosages prescribed to the participant and all dose changes during the study were to be recorded for assessment of participants who successfully tapered off of all corticosteroids. Participants who completely tapered off corticosteroids refer to those who permanently discontinued steroids as per the dose administration panel and who did not restart steroids in the same interval. Participants who were tapered off and continued follow-up were also counted as being tapered off with 0 dose in subsequent intervals until they discontinued from the main treatment period or restarted steroid treatment.
- measure
- Percentage of Participants Successfully Tapered Off of All Corticosteroids
- time Frame
- up to Day 179
- description
- Defined as the cumulative incidence rate from competing risk analysis of MR from the date of randomization to hematologic malignancy relapse/recurrence.
- measure
- Cumulative Incidence of Malignancy Relapse/Recurrence (MR)
- time Frame
- Months 3, 6, 12, 18, 24, 30, and 36
Full study description
- brief 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).
Source references
- references
- citation
- Mahmoudjafari Z, Bhatt V, Xue Z, Locatelli F, Socie G, Zeiser R. 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. Ther Adv Hematol. 2026 May 19;17:20406207261442908. doi: 10.1177/20406207261442908. eCollection 2026.
- pmid
- 42180389
- type
- DERIVED
- citation
- Zeiser R, Russo D, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hamad N, Burock K, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F. Ruxolitinib in Patients With Corticosteroid-Refractory or Corticosteroid-Dependent Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of the Phase III REACH3 Study. J Clin Oncol. 2025 Aug 10;43(23):2566-2571. doi: 10.1200/JCO-24-02477. Epub 2025 Jun 25.
- pmid
- 40561385
- type
- DERIVED
- citation
- Mahmoudjafari Z, Kintsch E, Xue Z, Bhatt V, Galvin J, Locatelli F, Zeiser R. Impact of concomitant azoles on ruxolitinib treatment in patients with GVHD: post hoc analyses of REACH2 and REACH3. Blood Adv. 2025 Aug 26;9(16):4206-4216. doi: 10.1182/bloodadvances.2025016212.
- pmid
- 40472328
- type
- DERIVED
- citation
- Le RQ, Wang X, Zhang H, Li H, Przepiorka D, Vallejo J, Leong R, Ma L, Goldberg KB, Pazdur R, Theoret MR, De Claro A. FDA Approval Summary: Ruxolitinib for Treatment of Chronic Graft-Versus-Host Disease after Failure of One or Two Lines of Systemic Therapy. Oncologist. 2022 Jun 8;27(6):493-500. doi: 10.1093/oncolo/oyac042.
- pmid
- 35363318
- type
- DERIVED
- citation
- Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hollaender N, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F; REACH3 Investigators. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2021 Jul 15;385(3):228-238. doi: 10.1056/NEJMoa2033122.
- pmid
- 34260836
- type
- DERIVED
- citation
- Jagasia M, Zeiser R, Arbushites M, Delaite P, Gadbaw B, Bubnoff NV. Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an introduction to the REACH trials. Immunotherapy. 2018 Apr;10(5):391-402. doi: 10.2217/imt-2017-0156. Epub 2018 Jan 10.
- pmid
- 29316837
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- Below is a display of the efficacy results of the adequate and well‑controlled studies of JAKAFI in adult and pediatric patients with cGVHD. Study 5 (REACH-3; NCT03112603) was a randomized, open-label, multicenter study of JAKAFI in comparison to BAT for treatment of corticosteroid-refractory cGVHD after allogeneic stem cell tra
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Preserved source evidence · Not medical advice