Leukemia, Myelomonocytic, Chronic, Myelodysplasia, Myelodysplastic Syndromes, Myelomonocytic
Conditions
Keywords
Lonafarnib
Brief summary
The purpose of this study is to assess the benefit of lonafarnib (versus placebo) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML). Benefit will be measured by achievement of platelet transfusion independence for at least 8-consecutive weeks, and without simultaneous worsening of hemoglobin and/or need for red blood cell (RBC) transfusion. Additional endpoints will be hematologic response (which includes complete remission, partial remission, hematologic improvement), number of RBC transfusions, bleeding events, infections and safety.
Interventions
DRUGLonafarnib
200 mg twice daily (BID, ie, approximately 12 hours apart with food), oral, continuously, or until unacceptable toxicity or transformation to AML, or disease progression, or other discontinuation criteria
OTHERPlacebo
BID, oral, continuously, or until unacceptable toxicity or transformation to AML, or disease progression, or other discontinuation criteria
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed MDS (RA, RARS, RAEB, RAEB-T) or CMML according to FAB classification. * Platelet transfusion dependence (requiring 1 to 8 platelet transfusion events every 4 week period (Day 84 to Day 57, Day 56 to Day 29, and Day 28 to Day 1) over an 8-week retrospective and 4-week prospective screening period). * The individual number of platelet transfusion events during the three 4-weekly periods (Day 84 to Day -57; Day -56 to Day 29; Day -28 to Day -1) must not differ by greater more than 2 from the average number of platelet transfusion events during the 12 week screening period. * If the subject is RBC transfusion dependent, the number of RBC transfusion events during the three 4-weekly periods (Days -84 to -57; Day -56 to Day 29 and Day -28 to Day -1) must not differ by more than 2 from the average number of RBC transfusion events during this 12 week screening period. ECOG PS 0-2.
Exclusion criteria
* Subjects with chemotherapy/radiotherapy-associated secondary MDS. * \<12 Weeks (prior to Day-1 Randomization) from any investigational drug use, any chemotherapy, radiotherapy, immunotherapy and any other treatment or MDS/CMML other than best supportive care. * Hx of bone-marrow or peripheral stem-cell transplantation or treatment with donor lymphocyte infusion. * Hx of AML. * Known hx of immune thrombocytopenic purpura. * Marked baseline prolongation of QTc interval, CTCAE Grade \>=1. * Use of ketokonazole within 72 hours prior to study drug administration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects who achieved platelet transfusion independence for any 8-consecutive week period after randomization without worsening of RBC transfusion requirements or hemoglobin (untransfused) during the same 8-consecutive-week period. | Any 8-consecutive week period after randomization |
Secondary
| Measure | Time frame |
|---|---|
| Hematologic response rate (CR, PR, HI), number of RBC transfusion events during a 4-week period, active bleeding events (number and severity), number of CTCAE Grade 3 and 4 infections and days of acute intervention, and safety. | Any 8-consecutive week period after randomization |
Outcome results
None listed