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)

Incyte

Status and phase: Completed; Phase 3

Conditions: Graft-versus-host Disease (GVHD)

Treatments: Drug: Infliximab; Drug: Ibrutinib; Drug: Extracorporeal photopheresis (ECP); Drug: Pentostatin; Drug: Rituximab; Drug: Mycophenolate mofetil (MMF); Drug: Ruxolitinib; Drug: Low-dose methotrexate (MTX); Drug: Imatinib; Drug: mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03112603

2016-004432-38 (EudraCT Number)

INCB 18424-365 (REACH3)

CINC424D2301 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 330 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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330 participants in 2 patient groups

Ruxolitinib

Experimental group

Description:

Ruxolitinib for the treatment period and extension period.

Treatment:

Drug: Ruxolitinib

Best Available Therapy

Active Comparator group

Description:

Best available therapy for the treatment period and extension period, with optional crossover to ruxolitinib after Cycle 6.

Treatment:

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

Drug: Imatinib

Drug: Low-dose methotrexate (MTX)

Drug: Rituximab

Drug: Mycophenolate mofetil (MMF)

Drug: Pentostatin

Drug: Extracorporeal photopheresis (ECP)

Drug: Ibrutinib

Drug: Infliximab