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)

• Register: ClinicalTrials.gov
• Last refreshed on: 2 August 2023
• Main ID: NCT03112603
• Date of registration: 04/04/2017
• Prospective Registration: Yes
• Primary sponsor: Incyte Corporation
• Public title: 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)
• Scientific title: A Phase III Randomized Open-label Multi-center Study of Ruxolitinib vs. Best Available Therapy in Patients With Corticosteroid-refractory Chronic Graft vs Host Disease After Allogeneic Stem Cell Transplantation (REACH3)
• Date of first enrolment: June 29, 2017
• Target sample size: 330
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03112603
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Jordan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Saudi Arabia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Rodica Morariu-Zamfir
• Affiliation: Incyte Corporation

Key inclusion & exclusion 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



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Graft-versus-host Disease (GVHD)

Intervention(s)

Drug: Low-dose methotrexate (MTX)

Drug: Ibrutinib

Drug: mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus)

Drug: Rituximab

Drug: Extracorporeal photopheresis (ECP)

Drug: Imatinib

Drug: Infliximab

Drug: Mycophenolate mofetil (MMF)

Drug: Ruxolitinib

Drug: Pentostatin

Primary Outcome(s)

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 Outcome(s)

AUCinf of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses [Time Frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose]

CL/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses [Time Frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose]

Vz/F of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses [Time Frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose]

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)]

AUClast of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses [Time Frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose]

Cumulative Incidence of Malignancy Relapse/Recurrence (MR) [Time Frame: Months 3, 6, 12, 18, 24, 30, and 36]

Duration of Response Through Study Completion [Time Frame: from first response to LPLV (approximately 5 years)]

Number of Participants With Any Treatment-emergent Adverse Event (TEAE) [Time Frame: from Baseline to LPLV (approximately 5 years)]

ORR at the End of Cycle 3 [Time Frame: Cycle 4 Day 1 (each cycle was comprised of 4 weeks)]

Best Overall Response (BOR) at Cycle 7 Day 1 [Time Frame: up to Cycle 7 Day 1 (each cycle was comprised of 4 weeks)]

Change From Baseline in EQ-5D-5L [Time Frame: Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks)]

Change From Baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) [Time Frame: Baseline; up to Cycle 39 Day 1 (each cycle was comprised of 4 weeks)]

Cmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses [Time Frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose]

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)]

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)]

Rate of FFS at Study Completion [Time Frame: From Baseline to Last Participant Last Visit (LPLV) (approximately 5 years)]

t1/2 of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses [Time Frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose]

Utilization of Medical Resources [Time Frame: from Baseline to LPLV (approximately 5 years)]

Cumulative Incidence of Non-relapse Mortality (NRM) [Time Frame: Months 3, 6, 12, 18, 24, 30, and 36]

Percentage of Participants With a = 50% Reduction in Daily Corticosteroid Dose [Time Frame: from Day 15 up to Day 182]

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)]

Tmax of Ruxolitinib After Single (Cycle 1 Day 1) and Multiple (Cycle 1 Day 15) Doses [Time Frame: Extensive Sampling Schedule: Cycle 1 Days 1 and 15: predose; 0.5, 1, 1.5, 4, 6, and 9 hours post-dose. Sparse Sampling Schedule: Cycle 1 Days 1 and 15: predose; 1.5 hours post-dose]

Percentage of Participants Successfully Tapered Off of All Corticosteroids [Time Frame: up to Day 179]

Secondary ID(s)

INCB 18424-365 (REACH3)

CINC424D2301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 15/04/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03112603