Phase II, multi-center, open-label, single-arm clinical trial evaluating the efficacy and safety of Mycophenolate Mofetil in patients with high-grade locally advanced or metastatic osteosarcoma (ESMMO): rationale and design of the ESMMO trial

Table 2 Hematological and non-hematological criteria for suggested dose modification of mycophenolate mofetil

Toxicity^(a)	Hold study treatment	Dose modification
Hematological criteria
Grade 4 bone marrow hypocellular	No^(b)	Decrease one dose level^(c)
Grade 4 febrile neutropenia	No^(b)	Decrease one dose level^(c)
Grade 4 neutrophil count decreased	No^(b)	Decrease one dose level^(c)
≥ Grade 3 of other hematologic toxicities	No^(b)	Decrease one dose level^(c)
Sepsis & any Grade 3 infection	Yes until ≤ Grade 2^(d)	Resume at one dose level lower^(c)
Sepsis & any Grade 4 infection	Yes until ≤ Grade 2^(d)	Resume at two dose level lower^(c)
Non-hematological criteria
Grade 3, except for: delayed puberty, growth suppression, breast atrophy, erectile dysfunction, diarrhea^(e), vomiting^(e), and AST/ALT increased or other biochemical laboratory abnormalities without any clinically significant sequelae	No^(b)	Decrease one dose level^(c)
Any Grade 4 toxicity	No^(b)	Decrease two dose level^(c)

^(a) If no recovery (until ≤ Grade 2) is noted after 7 days of dose modification of mycophenolate mofetil, that event will be considered as another toxicity requiring one more dose reduction; ^(b) Study treatment may be held whenever clinically needed (at the discretion of the PI and study team); ^(c) If more than 3 dose reductions are required, study treatment may be discontinued unless there is reasonable evidence of clinical benefit to justify continuation in the study; ^(d) If no recovery (until ≤ Grade 2) is noted after a 28-day delay, study treatment will be discontinued unless there is reasonable evidence of clinical benefit to justify continuation in the study; ^(e) Only if it occurs despite maximal medical treatment

ISSN: 1471-2407