Phase 1 Weekly Dosing of SCH 727965 in Patients With Advanced Cancer (Study P04629AM6)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumors, Lymphoma, Non-Hodgkin, Multiple Myeloma, Leukemia, Lymphocytic, Chronic. B-Cell

Intervention / Treatment
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* Drug: SCH 727965


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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 727965. 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: serum free light chain ratio greater than 5 times the normal ratio limit; and/or 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. 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 727965. Known HIV infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advanced solid tumors<br>Participants with advanced solid tumors treated with SCH 727965 in dose-escalation cohorts | Drug: SCH 727965<br>* Dose escalation of SCH 727965 IV administered in 28-day cycles, on Days 1, 8, and 15 of each 28-day cycle.<br>|
| Experimental: Non-Hodgkin's lymphoma and multiple myeloma<br>Participants with non-Hodgkin's lymphoma or multiple myeloma treated with SCH 727965 | Drug: SCH 727965<br>* Dose escalation of SCH 727965 IV administered in 28-day cycles, on Days 1, 8, and 15 of each 28-day cycle.<br>|
| Experimental: B cell chronic lymphocytic leukemia<br>Participants with B-cell chronic lymphocytic leukemia treated with SCH 727965 in dose-escalation cohorts | Drug: SCH 727965<br>* Dose escalation of SCH 727965 IV administered in 28-day cycles, on Days 1, 8, and 15 of each 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of SCH 727965, including maximum administered dose and dose-limiting toxicity. |  | 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. |  | End of trial |