PMID- 25217392
OWN - NLM
STAT- MEDLINE
DCOM- 20150129
LR  - 20211203
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 74
IP  - 5
DP  - 2014 Nov
TI  - Clinical study of the novel cyclin-dependent kinase inhibitor dinaciclib in 
      combination with rituximab in relapsed/refractory chronic lymphocytic leukemia 
      patients.
PG  - 1057-64
LID - 10.1007/s00280-014-2583-9 [doi]
AB  - PURPOSE: Dinaciclib is a novel selective inhibitor of cyclin-dependent kinase 
      (CDK)1, CDK2, CDK5, and CDK9. We conducted a phase I study to investigate the 
      effects of dinaciclib when administered with rituximab. METHODS: In this phase I 
      nonrandomized dose-escalation 3 + 3 trial, patients with relapsed/refractory 
      chronic lymphocytic leukemia (CLL) were treated with dinaciclib and rituximab. 
      Dinaciclib was administered intravenously (IV) over 2 h on days 1, 8 and 15 in 
      cycles 2-13 (28-day cycles). Rituximab 375 mg/m(2) was administered IV on days 1, 
      8, 15 and 22 in cycle 1 (28-day cycle) and on day 1 during cycle 3-13. Rituximab 
      was not administered in cycle 2. Rituximab and dinaciclib were given alone in 
      cycles 1 and 2, respectively, and in combination in cycles 3-13. Primary 
      objectives included determination of the recommended phase II dose of dinaciclib 
      and evaluation of pharmacokinetics (PK) when administered with rituximab. 
      RESULTS: Five patients completed the study due to early termination. All 
      presented with drug-related adverse events (AEs), but no dose-limiting toxicities 
      were observed. The most commonly observed toxicities included hematological, 
      digestive and metabolic AEs. However, no tumor lysis syndrome has been reported 
      in the study. Four patients achieved stable disease, and one patient achieved 
      complete response according to 2008 iwCLL criteria at cycle 3. PK samples were 
      collected from 5 patients, and no obvious interaction between dinaciclib and 
      rituximab was observed. CONCLUSIONS: Limited data from this study shows 
      dinaciclib in combination with rituximab was well tolerated and revealed 
      encouraging clinical activity in relapsed/refractory CLL patients.
FAU - Fabre, Claire
AU  - Fabre C
AD  - Department of Medical Oncology, Institut Curie, 26 Rue d'Ulm, 75005, Paris, 
      France, fabre-claire@wanadoo.fr.
FAU - Gobbi, Marco
AU  - Gobbi M
FAU - Ezzili, Cyrine
AU  - Ezzili C
FAU - Zoubir, Mustapha
AU  - Zoubir M
FAU - Sablin, Marie-Paule
AU  - Sablin MP
FAU - Small, Karen
AU  - Small K
FAU - Im, Ellie
AU  - Im E
FAU - Shinwari, Nabeegha
AU  - Shinwari N
FAU - Zhang, Da
AU  - Zhang D
FAU - Zhou, Honghong
AU  - Zhou H
FAU - Le Tourneau, Christophe
AU  - Le Tourneau C
LA  - eng
SI  - ClinicalTrials.gov/NCT01650727
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140913
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antibodies, Monoclonal, Murine-Derived)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Cyclic N-Oxides)
RN  - 0 (Indolizines)
RN  - 0 (Pyridinium Compounds)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 4V8ECV0NBQ (dinaciclib)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Administration, Intravenous
MH  - Aged
MH  - Anemia/chemically induced
MH  - Antibodies, Monoclonal, Murine-Derived/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Area Under Curve
MH  - Asthenia/chemically induced
MH  - Bridged Bicyclo Compounds, Heterocyclic/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Cyclic N-Oxides
MH  - Cyclin-Dependent Kinases/*antagonists & inhibitors/metabolism
MH  - Diarrhea/chemically induced
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Indolizines
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/metabolism/pathology
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local
MH  - Pyridinium Compounds/administration & dosage/adverse effects/pharmacokinetics
MH  - Rituximab
MH  - Treatment Outcome
EDAT- 2014/09/14 06:00
MHDA- 2015/01/30 06:00
CRDT- 2014/09/14 06:00
PHST- 2014/07/24 00:00 [received]
PHST- 2014/08/30 00:00 [accepted]
PHST- 2014/09/14 06:00 [entrez]
PHST- 2014/09/14 06:00 [pubmed]
PHST- 2015/01/30 06:00 [medline]
AID - 10.1007/s00280-014-2583-9 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2014 Nov;74(5):1057-64. doi: 
      10.1007/s00280-014-2583-9. Epub 2014 Sep 13.