11 mg m2 infusion dose died of cardiac arrest, one subject treated with the 14

The primary objectives of this study were to determine ABT-888 PARP 阻害剤 the safety, tolerability, maximum administered dose, dose limiting toxicity, and recommended phase 2 dose of dinaciclib, and to assess pharmacodynamic effects using an ex vivo lymphocyte stimulation assay, Rb protein phosphorylation, and 18 F fluorodeoxyglucose posi tron emission tomography computed tomography, Methods Study population This was a nonrandomized, open label, phase 1 trial of adult subjects with histologically proven solid tumors, non Hodgkins lymphoma, or multiple myeloma refractory to standard therapy or for which there is no standard therapy. Subjects had Eastern Cooperative Oncology Group performance statuses of 0, 1 or 2 and had to have adequate organ function and labora tory parameters.<br><br> Subjects were excluded from the study if they had symptomatic brain metastases or primary central nervous system malignancy. Subjects must not have re ceived any radiation therapy within 4 weeks prior to the start of treatment with dinaciclib, or have had a history of radiation therapy to greater than 25% of the total bone marrow. In addition, Afatinib 439081-18-2 subjects could not have received pre vious treatment with an investigational drug or biologic or hormonal therapy within 4 weeks of study treatment, mitomycin, nitrosourea, nilutamide, or bicalutamide within 6 weeks of study treatment, or cytochrome P450 3A4 inhibitors or inducers within 1 week of study treat ment. Known human immunodeficiency virus and HIV related malignancy were also exclusion criteria.<br><br> The study was conducted in accordance with good clin ical practice and the Declaration of Helsinki concerning written informed consent and the protection of rights of human subjects. Before study initiation, the clinical study protocol, any amendments, and the written informed AG-1478 153436-53-4 con sent forms were reviewed and approved by an independ ent review board at each study site. Each subject had to provide written informed consent before undergoing any study related activities. Study endpoints and treatment plan The primary endpoints of the study were to determine the safety, tolerability, MAD, DLT, and the RP2D of dinaciclib, and to assess the PD effects of dinaciclib on peripheral blood lymphocytes.<br><br> Secondary endpoints in cluded determining the pharmacokinetic profile of dinaciclib following a single dose and following the third weekly dose, assessment of Rb protein phosphorylation in subject skin biopsy samples, preliminary evaluation of the antitumor activity of dinaciclib, and assessment of tumor metabolic changes in response to dinaciclib treat ment via use of FDG PET CT. Dinaciclib was administered as a 2 hour IV infusion on days 1, 8, and 15 of a 28 day cycle. The 2 hour duration of IV infusion was selected based on previous nonclinical toxicity toxicokinetic studies conducted in dogs that dem onstrated acute toxicity following IV push.