-Participants will take ruxolitinib twice every day

Other Cancer

Ruxolitinib blocks certain proteins called tyrosine kinases. Specifically, it blocks tyrosine kinases called JAK2. it's believe that ruxolitinib may lower the rate of GVHD through its ability to block the JAK2 pathway since this pathway can lead to inflammation in the body

ruxolitinib

Massachusetts General Hospital

Ruxolitinib for Bronchiolitis Obliterans Syndrome (BOS) After Allogeneic Hematopoietic Cell Transplantation (HCT)

A Phase II Study of Ruxolitinib for Bronchiolitis Obliterans Syndrome (BOS) After Allogeneic Hematopoietic Cell Transplantation (HCT)

The proportion of participants with a sustained, absolute FEV1 increase by ≥ 10% after 3 months of treatment with ruxolitinib (compared to baseline measure prior to study enrollment) among participants with newly diagnosed Bronchiolitis Obliterans Syndrome BOS.

The proportion of participants who do not experience a sustained, absolute decrease in FEV1 by ≥ 10% after 3 months of treatment with ruxolitinib (compared to baseline measure prior to study enrollment) among participants with established Bronchiolitis Obliterans Syndrome BOS.

Change in pulmonary function test (PFT) measurements.

Improvements in chronic GVHD organ manifestations will be categorized according to the NIH chronic GVHD consensus criteria.

cGVHD progression-free survival is defined as the time from registration to the earlier of progression of chronic GVHD or death due to any cause. Participants alive without cGVHD progression are censored at the date of last disease evaluation.

Adverse events are graded according to Common Terminology Criteria for Adverse Events (CTCAE v4).

Zachariah Michael DeFilipp

Principal Investigator

Incyte Corporation

Nintedanib 150 mg tablet by mouth twice daily for 24 months.

Placebo tablet by mouth twice daily for 24 months

Idiopathic Pulmonary Fibrosis

Lung Transplant; Complications

Nintedanib

Placebo Oral Tablet

Temple University Hospital

Continuation of Nintedanib After Single Lung Transplantation in IPF Subjects

Nintedanib Plus Usual Transplant Care Compared to Usual Transplant Care Alone After Single Lung Transplantation in Patients With Idiopathic Pulmonary Fibrosis: a Pilot Randomized Controlled Trial

Change in forced expiratory volume in 1 second (FEV1)

Incidence of bronchiolitis obliterans syndrome (BOS)

Incidence of surgical anastomosis bronchial stenosis

Incidence of acute cellular rejection of lung allograft

Study drug discontinuation rate due to adverse drug event

Incidence of adverse drug events (i.e. elevation of liver transaminases greater than 3 times the upper limit of normal, diarrhea, nausea, vomiting, anorexia, GERD)

Change in serum biomarker concentration for VEGF (pg/mL)

Change in BAL concentration for VEGF (pg/mL)

Change in serum concentration for VEGF (pg/mL)

Change in serum concentration for FGF (pg/mL)

Change in BAL concentration for FGF (pg/mL)

Change in BAL biomarker concentration for FGF (pg/mL)

Change in serum concentration for PDGF (pg/mL)

Change in BAL biomarker concentration for PDGF (pg/mL)

Change in serum biomarker concentration for PDGF (pg/mL)

CD4 T cell concentration in peripheral blood (cells/µL)

CD8 T cell concentration in peripheral blood (cells/µL)

Macrophage concentration in peripheral blood (cells/µL)

Neutrophil concentration in peripheral blood (cells/µL)

Survival and time to death/cause of death (if applicable) of study subjects

Temple University

Boehringer Ingelheim

Eligible LTx recipients with BOS receive Nintedanib treatment at a dose of 150 mg twice daily (bid) for 6 months

Eligible LTx recipients with BOS receive Nintedanib 150 mg BID matching placebo treatment for 6 months

Lung-transplant Recipients

Placebo

Foch Hospital

Nintedanib in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome Grade 1-2

A Multi-center, Randomised, Double-blind Trial of Nintedanib in Lung Transplant (LTx) Recipients With Bronchiolitis Obliterans Syndrome (BOS) Grade 1-2

The absolute difference of FEV1 in mL over 6 months of treatment defined by the rate of decline between inclusion (Visit 1) and month 6 (Visit 4) will be compared between Nintedanib versus Placebo groups

Nintedanib efficacy on exercise tolerance will be assessed by the absolute change from baseline in the 6-min Walking Test at month 6 in Nintedanib group compared to Placebo group

Nintedanib efficacy on quality of life improvement will be assessed by the absolute change from baseline in SGRQ (Saint George's Respiratory Questionnaire) total score at month 6 in Nintedanib group compared to Placebo group

Nintedanib efficacy to hamper FEV1 decrease will be assessed by the absolute change of FEV1 in mL at month 6 by a repeated FEV1 measurements (at month 0, month 1, month 3, month 6) in Nintedanib group compared to Placebo group

Nintedanib efficacity to hamper progression of BOS will be assessed by the proportion of patients with change in BOS grade and graft failure (defined as death or retransplantation) in Nintedanib group compared to Placebo group

Nintedanib efficacity on the change of Oxygen saturation will be assessed by the absolute change from baseline in Oxygen saturation (expressed in percent) rest evaluated from baseline at month 6 in Nintedanib group compared to Placebo group

Nintedanib tolerance in lung-transplant recipients over 6 months will be assessed in comparing occurrence of adverse events between both arms (Nintedanib vs Placebo)

Explanatory parameters of fibrotic pathways will be assessed by absolute changes of biomarkers of alveolar cells injury (Krebs von den Lungen-6 (KL6), surfactant apoprotein D (SPD), and growth factors as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)) since baseline at month 6

Assistance Publique - Hôpitaux de Paris

3 patients (pts) will receive Nilotinib 200 mg daily dose. If no dose-limiting toxicity, the next 3 pts will be treated with next dose of Nilotinib 300 mg daily dose.
Doses will not be escalated beyond 600 or below 200 mg/die. The dose estimated as the MTD in phase I will be used for phase II.

Chronic Graft Versus Host Disease

Maximum tolerated dosage (MTD) will be defined in Phase I. First 3 patients (pts) will receive Nilotinib 200mg daily dose. If no dose limiting toxicities after at least 1month the next 3 pts will be treated with 300mg. If are>=2 dose limiting toxicities the Phase I will end and MTD will be defined as the next lower dosage. If they will observe 1dose limiting toxicities, they will treat other 3 pts (same dosage); if there isn't dose limiting toxicity, they will increase the dosage in the next cohort; but if they will observe another dose limiting toxicity (tot limiting toxicities 2/6 pts), the study will continue using the previous dose. MTD will be considered the maximum dosage used to treat 6 pts achieving at most 1 dose limiting toxicities, or the previous dosage if with this dosage they we will achieve 2 dose limiting toxicities. Doses will not be escalated beyond >600 or <200mg/die The MTD will be used for phase II

nilotinib

Chaim Sheba Medical Center

Clinica di Ematologia - Ospedali Riuniti di Ancona

S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle

Trapianti Midollo Osseo - Div. di Ematologia 2 - Ospedale S. Martino

Ospedale Panico

Divisione di Ematologia - Istituto Nazionale dei Tumori

Ospedale Niguarda Ca' Grande

U.O. Ematologia I - Centro Trapianti di Midollo - Ospedale Maggiore - Policlinico Mangiagalli e Regina Elena

Ospedale San Carlo

Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli

Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza

Clinica Ematologica - AOU Santa Maria Della Misericordia

Phase I/II for Safety and Efficacy of Nilotinib in a Population Steroid-refractory/or Steroid-dependent cGVHD

Prospective, Phase I/II, Non-randomized, Open Label, Multicenter Study to Determine Safety and Efficacy of Nilotinib in a Population With Steroid-refractory/or Steroid-dependent cGVHD.

Primary is DLT - occurrence of any grade >3 toxicity after at least one month of treatment.

Overall Response Rate (ORR)is defined as an Objective improvement at sixth month, and includes at least 1 of the following criteria:
At least 50% reduction of body surface area involved;
Reduction (at least 20%) of skin sclerosis, measured by Rodnan score
Improvement>1 point in functional pulmonary tests, evaluated by LFS score;
>50% steroid reduction (for at least 4 weeks)

Number of patients experiencing failure, from date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months after the enrolment.

Number of patients alive from date of registration until the date of death from any cause, assessed up to 24 months after the enrolment

To assess how Nilotinib could interact with the putative pathogenetic pathways of the cGvHD:
Presence and activity of auto-antibodies stimulating PDGF-R baseline and during treatment;
Modifications of fibroblast (from skin biopsies from patients with skin involvement) characteristics (in terms of: ROS output, modification of both the PDGF-R and the TGFΒ downstream and collagen production)before and after treatment.
Quantitative and qualitative modifications of the immune cell populations.
Plasma levels of Nilotinib in order to find relationship between clinical improvement and plasma Nilotinib dosage.

bronchiolitis/tyrosine

Ruxolitinib for Bronchiolitis Obliterans Syndrome (BOS) After Allogeneic Hematopoietic Cell Transplantation (HCT)

Continuation of Nintedanib After Single Lung Transplantation in IPF Subjects

Nintedanib in Lung Transplant Recipients With Bronchiolitis Obliterans Syndrome Grade 1-2

Phase I/II for Safety and Efficacy of Nilotinib in a Population Steroid-refractory/or Steroid-dependent cGVHD

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