There are 2 clinical trials
Chronic Graft versus Host Disease (cGvHD) has been identified as the leading cause of late non-relapse mortality in Hemopoietic Stem Cell Transplant (HSCT) survivors. Up to now a standard satisfactory treatment for these patients does not exist. cGVHD is an immune-mediated disease, resulting from a complex interaction between donor and recipient adaptive immunity, but its exact pathogenesis is still incompletely defined. The purpose of this study is to determine safety and efficacy of Nilotinib in a population with steroid-refractory/or steroid-dependent cGvHD with a phase I study. In phase II the MTD will be used to define the efficacy of Nilotinib in a cGvHD steroid- refractory or steroid dependent population, with the same characteristics of the previously Imatinib-treated population.
It has to be noticed that in all the proliferation assays the concentration at which 50% of effect is inhibited of Nilotinib is lower than 50 nM, apart from the two BCR-ABL mutants (E255K and E255V) where the IC50 is 600 to 700 nM. --- E255K --- --- E255V ---
Description: Primary is DLT - occurrence of any grade >3 toxicity after at least one month of treatment.
Measure: Dose Limiting Toxicity (DLT) Time: within 6 months since the start of treatmentDescription: 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)
Measure: Overall Response Rate (ORR) Time: 6 months after date of start of NilotinibDescription: 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.
Measure: Time to treatment Failure (TTF) Time: participants will be followed for the duration of the 6 months of treatment, and for the follow-up for expected average of 12 monthsDescription: Number of patients alive from date of registration until the date of death from any cause, assessed up to 24 months after the enrolment
Measure: Overall Survival (OS) Time: participants will be followed for the duration of the 6 months of treatment, and for the follow-up for expected average of 12 monthsDescription: 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.
Measure: BIOLOGICAL TASKS Time: Every 6 months starting from baseline (at enrolment), along the duration of the 6 months of treatment, and for the follow-up for expected average of 12 monthsDescribe the purpose of the study: This study aims to evaluate the improvement of Dasatinib-related adverse events and to evaluate the treatment effect and safety by measuring the genetic response of nilotinib with nilotinib 400mg BID for 12 months in Philadelphia chromosome-positive chronic myeloid leukemia patients intolerant to Dasatinib.
- Potassium ≥ LLN- Magnesium ≥ LLN- Phosphorus ≥ LLN 7. Voluntary, signed and dated informed consent prior to any study procedures being performed Exclusion Criteria: 1. Subjects with the T315I mutation 2. Mutation known to be associated with low sensitivity to nilotinib(e.g., Y253H, E255K, E255V, F359V), 3. Cardiac function abnormalities as follows are found. --- T315I --- --- Y253H --- --- E255K --- --- E255V ---