A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Cyclin-Dependent Kinase (CDK) Inhibitor SCH 727965 Administered Weekly in Subjects With Advanced Malignancies
- Age >=18 years, either sex, any race.
- Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
- There must be no known standard therapy, or disease must be refractory to standard
- Adequate hematologic, renal, and hepatic organ function and laboratory parameters
- For advanced solid tumors, non-Hodgkin's lymphoma, or multiple myeloma:
- Participants must have histologically proven solid tumors, non-Hodgkin's
lymphoma, or multiple myeloma.
- Evaluable malignancy must be present by computed tomography or magnetic
resonance imaging, obtained within 4 weeks prior to the start of treatment with
- Subjects with multiple myeloma must have measurable disease defined as:
- Serum monoclonal protein greater than 0.5 g/dL or urine light chain excretion of
greater than 0.2 g/24-hour obtained within 4 weeks prior to the start of
- Participants with lower M protein values or nonsecretory myeloma are eligible if
measurable disease can be established within 4 weeks prior to start of
treatment, such as:
- serum free light chain ratio greater than 5 times the normal ratio limit;
- measurable soft tissue plasmacytoma greater than 2 cm, by either physical
examination and/or applicable radiographs; and/or
- bone marrow involvement greater than 30%.
- For B-cell chronic lymphocytic leukemia (B-CLL):
- Diagnosis of B-CLL according to the National Cancer Institute Working Group
(NCI-WG) criteria or a histological diagnosis of small lymphocytic lymphoma.
- Disease must be evaluable according to NCI-WG response criteria.
- Symptomatic brain metastases or primary central nervous system malignancy.
- Previous radiation therapy to >25% of the total bone marrow.
- Previous treatment with SCH 727965.
- Known HIV infection.