Abstract
We conducted a phase I–II study to evaluate Nilotinib (NIL) safety and pharmacokinetics in 22 SR-cGVHD patients; we also evaluated ORR by using in parallel NIH criteria and an exploratory approach, combining objective improvement (OI) without failure criteria (GITMO criteria). Results: 22 patients were enrolled. After dose escalation up to 600 mg/day, MTD was not reached. Main toxicities were asthenia, headache, nausea, pruritus, cramps, and mild anemia. Mean and median plasma concentrations of NIL (C-NIL) were 817 (SD ± 450) and 773 ng/ml. ORR at 6 months, according to 2005 and 2014 NIH and GITMO criteria were 27.8%, 22.2%, and 55.6% respectively; close correspondence has been observed for ORR, according to 2014 NIH criteria, both assessed in a conventional way and assisted by dedicated software (CROSY). At 48 months OS was 75% while FFS, according to NIH and GITMO criteria, was 30 and 25%. In conclusion the safety profile of NIL and long-term outcome makes NIL an attractive option in SR-cGVHD. Exploratory GITMO criteria could represent an alternative tool for easy response evaluation in patients with prevalent skin and lung involvement, but require validation in a larger population; CROSY software showed excellent reliability in capturing ORR according to the 2014 NIH criteria. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Original language | English |
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Pages (from-to) | 2077-2086 |
Number of pages | 10 |
Journal | Bone Marrow Transplant. |
Volume | 55 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2020 |
Keywords
- cyclosporine
- mycophenolate mofetil
- nilotinib
- prednisone
- steroid
- tacrolimus
- adult
- aged
- anemia
- Article
- asthenia
- bronchopneumonia
- chronic graft versus host disease
- clinical article
- clinical effectiveness
- disease classification
- drug blood level
- drug dose comparison
- drug megadose
- drug safety
- exploratory research
- failure free survival
- female
- headache
- human
- human cell
- low drug dose
- male
- maximum tolerated dose
- muscle cramp
- nausea
- parallel design
- pharmacokinetic parameters
- phase 1 clinical trial
- phase 2 clinical trial
- photopheresis
- pneumococcal meningitis
- pneumonia
- priority journal
- progression free survival
- prospective study
- pruritus
- tonsillitis
- treatment duration
- treatment outcome
- treatment response
- validation study