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
Overview
- Phase
- Phase 1
- Intervention
- SCH 727965
- Conditions
- Solid Tumors
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 123
- Primary Endpoint
- Safety and tolerability of SCH 727965, including maximum administered dose and dose-limiting toxicity.
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The study will evaluate the safety, tolerability, maximum administered dose, and dose limiting toxicity of SCH 727965 administered as an intravenous infusion on Days 1, 8 and 15 of each 28 day cycle in participants with solid tumors, non Hodgkins lymphoma, multiple myeloma or chronic lymphocytic leukemia.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \>=18 years, either sex, any race.
- •Eastern Cooperative Oncology Group performance status of 0, 1, or
- •There must be no known standard therapy, or disease must be refractory to standard therapy
- •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 SCH
- •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 treatment.
- •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:
Exclusion Criteria
- •Symptomatic brain metastases or primary central nervous system malignancy.
- •Previous radiation therapy to \>25% of the total bone marrow.
- •Previous treatment with SCH
- •Known HIV infection.
Arms & Interventions
Advanced solid tumors
Participants with advanced solid tumors treated with SCH 727965 in dose-escalation cohorts
Intervention: SCH 727965
Non-Hodgkin's lymphoma and multiple myeloma
Participants with non-Hodgkin's lymphoma or multiple myeloma treated with SCH 727965
Intervention: SCH 727965
B cell chronic lymphocytic leukemia
Participants with B-cell chronic lymphocytic leukemia treated with SCH 727965 in dose-escalation cohorts
Intervention: SCH 727965
Outcomes
Primary Outcomes
Safety and tolerability of SCH 727965, including maximum administered dose and dose-limiting toxicity.
Time Frame: End of trial
In participants with advanced solid tumors, non Hodgkin's lymphoma or multiple myeloma, pharmacodynamic effects of SCH 727965 with an ex vivo lymphocyte stimulation assay of participant's peripheral blood lymphocytes.
Time Frame: End of trial