Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma
Jazyk angličtina Země Spojené státy americké Médium electronic
Typ dokumentu klinické zkoušky, fáze I, klinické zkoušky, fáze II, časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P30 CA015083
NCI NIH HHS - United States
P50 CA186781
NCI NIH HHS - United States
PubMed
30061664
PubMed Central
PMC6066484
DOI
10.1038/s41408-018-0106-3
PII: 10.1038/s41408-018-0106-3
Knihovny.cz E-zdroje
- MeSH
- cyklofosfamid aplikace a dávkování MeSH
- dexamethason aplikace a dávkování MeSH
- dospělí MeSH
- glycin aplikace a dávkování analogy a deriváty MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom diagnóza farmakoterapie mortalita MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sloučeniny boru aplikace a dávkování MeSH
- staging nádorů MeSH
- transplantace hematopoetických kmenových buněk MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- cyklofosfamid MeSH
- dexamethason MeSH
- glycin MeSH
- ixazomib MeSH Prohlížeč
- sloučeniny boru MeSH
Ixazomib is the first oral proteasome inhibitor to enter the clinic. Given the efficacy of bortezomib in combination with cyclophosphamide and dexamethasone, we studied the combination of ixazomib, cyclophosphamide and dexamethasone (ICd) in newly diagnosed multiple myeloma (NDMM) and patients with measurable disease, irrespective of transplant eligibility, were enrolled. The phase 1 was to determine the maximum tolerated dose (MTD) of cyclophosphamide in the combination. Patients received ixazomib 4 mg (days 1, 8, 15), dexamethasone 40 mg (days 1, 8, 15, 22), and cyclophosphamide 300 or 400 mg/m2 days 1, 8, 15, 22; cycles were 28 days. We enrolled 51 patients, 10 in phase 1 and 41 patients in phase 2. The median age was 64.5 years (range: 41-88); 29% had high or intermediate risk FISH. The MTD was 400 mg/m2 of cyclophosphamide weekly. The best confirmed response in all 48 patients included ≥ partial response in 77%, including ≥ VGPR in 35%; 3 patients had a sCR. The response rate for all 48 evaluable patients at 4-cycles was 71%; the median time to response was 1.9 months. Common adverse events included cytopenias, fatigue and GI intolerance. ICd is a convenient, all oral combination that is well tolerated and effective in NDMM.
Department of Biostatistics Mayo Clinic Rochester MN USA
Division of Hematology and Oncology Mayo Clinic Phoenix AZ USA
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