Phase I/II for Safety and Efficacy of Nilotinib in a Population Steroid-refractory/or Steroid-dependent cGVHD (Nilo-cGVHD)
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|ClinicalTrials.gov Identifier: NCT01810718|
Recruitment Status : Completed
First Posted : March 13, 2013
Last Update Posted : July 6, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Graft Versus Host Disease||Drug: nilotinib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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.|
|Study Start Date :||November 2011|
|Actual Primary Completion Date :||February 2015|
|Actual Study Completion Date :||March 2016|
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.
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
- Dose Limiting Toxicity (DLT) [ Time Frame: within 6 months since the start of treatment ]Primary is DLT - occurrence of any grade >3 toxicity after at least one month of treatment.
- Overall Response Rate (ORR) [ Time Frame: 6 months after date of start of Nilotinib ]
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)
- Time to treatment Failure (TTF) [ Time Frame: participants will be followed for the duration of the 6 months of treatment, and for the follow-up for expected average of 12 months ]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.
- Overall Survival (OS) [ Time Frame: participants will be followed for the duration of the 6 months of treatment, and for the follow-up for expected average of 12 months ]Number of patients alive from date of registration until the date of death from any cause, assessed up to 24 months after the enrolment
- BIOLOGICAL TASKS [ Time Frame: 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 months ]
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01810718
|Chaim Sheba Medical Center|
|Tel Hashomer, Israel|
|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|
|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|
|Reggio Calabria, Italy|
|Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza|
|S. Giovanni Rotondo (FG), Italy|
|Clinica Ematologica - AOU Santa Maria Della Misericordia|
|Principal Investigator:||Attilio Olivieri, MD||Azienda Ospedaliero Universitaria OORR Umberto I - Marche|