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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)

Study of efficacy and safety of ruxolitinib vs. best available therapy (BAT) in patients with corticosteroid refractory chronic graft versus host disease

Yes

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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com.

Hirano Takamitsu

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

rinshoshiken.toroku2@novartis.com

Hirano Takamitsu

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

+81-120-003-293

rinshoshiken.toroku2@novartis.com

completed

Nov. 30, 2017

Interventional

Randomized, open label, multi center

treatment purpose

3

- Male or female patients =>12 years old at the time of signing the ICF
- Have undergone 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/mm3 and platelet count > 25,000/ mm3
- Patients with clinically diagnosed moderate to severe cGvHD according to NIH Consensus Criteria (Jagasia 2015) 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
- Patients 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 (Martin 2015) irrespective of the concomitant use of a calcineurin inhibitor, as
follows:
- A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week (or equivalent), 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 equivalent), OR
- Increase to prednisolone dose to >0.25 mg/kg/day after two unsuccessful attempt to taper the dose (or equivalent)
- Patient 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

- Patients who have received two or more systemic treatments 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 who were treated with prior JAK inhibitors for aGvHD; except when the patient 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
- Patients with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed
- SR-cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Patients 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

Both

steroid refractory chronic graft versus host disease(SR-cGvHD)

- Ruxolitinib will be administered to patients randomized to the study drug treatment arm at a starting dose of 10 mg orally BID, without regard to food.
- The BAT in this study will be selected by the Investigator prior to subject randomization among the following standard systemic treatments: extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, or ibrutinib.

efficacy
To compare the efficacy of ruxolitinib vs. Investigator choice Best Available Therapy (BAT) in patients with moderate or severe SR-cGvHD assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 visit

efficacy
To compare the rate of failure free survival (FFS)

July. 25, 2017