Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell
Conditions
Brief summary
Participants will be randomized to SCH 727965 or a comparator drug (bortezomib for mantle cell lymphoma \[MCL\] or alemtuzumab for B cell chronic lymphocytic leukemia \[B CLL\]). Part 1 of the study will determine the activity of SCH 727965 treatment in participants with MCL and participants with B-CLL. Part 2 of the study will determine the activity of SCH 727965 treatment in participants who experienced disease progression after standard treatment with the comparator drug during Part 1.
Interventions
DRUGSCH 727965
SCH 727965 50 mg/m2 IV on Day 1 of each 21-day cycle until disease progression.
DRUGBortezomib
Bortezomib 1.3 mg/m2 IV on Days 1, 4, 8, and 11 of each 21-day cycle until disease progression.
BIOLOGICALAlemtuzumab
Alemtuzumab dose-titrated to the goal maintenance dose of 30 mg/day IV or SC three times a week on alternate days for a total of 12 weeks.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>=18 years, either sex, any race. * Eastern Cooperative Oncology group performance status of 0 or 1. * Adequate hematologic, renal, and hepatic organ function and laboratory parameters. * For subjects with MCL: * Diagnosis of MCL according to the World Health Organization (WHO) criteria. * Received at least one prior chemotherapeutic regimen, but no more than two regimens including stem cell transplantation.. * Measurable or assessable disease by the Revised Response Criteria for Malignant Lymphoma. * For subjects with B-CLL * Documented B-CLL according to the National Cancer Institute Working Group (NCI-WG) criteria. * Received at least one prior alkylating agent-based regimen and one fludarabine- or pentostatin-containing regimen, but must not have received more than two prior regimens. * Measurable or assessable disease by NCI-WG criteria.
Exclusion criteria
* Known central nervous system involvement of MCL or B-CLL. * Previous treatment with SCH 727965 or other cyclin-dependent kinase inhibitors. * For MCL, previous treatment with bortezomib. * For B-CLL, previous treatment with alemtuzumab. * Known HIV infection. * Known active hepatitis B or C.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response rate of initial treatment with SCH 727965 in subjects with MCL or B-CLL. | Time to identified disease progression on SCH 727965 in Part 1 (approx. 6 months) |
| Response rate in subjects treated with SCH 727965 after disease progression on comparator drug. | Time to identified disease progression on SCH 727965 in Part 2 (approx. 6 months) |
Secondary
| Measure | Time frame |
|---|---|
| Time to disease progression for initial treatment with SCH 727965. | Time to identified disease progression on SCH 727965 in Part 1 (approx. 6 months) |
| Time to disease progression and response rate for treatment with the comparator drug. | Time to identified disease progression on comparator drug (bortezomib for MCL or alemtuzumab for B-CLL). |
| Response rate for treatment with the comparator drug. | Time to identified disease progression on comparator drug (bortezomib for MCL or alemtuzumab for B-CLL). |
| Time to disease progression in participants treated with SCH 727965 after disease progression on comparator drug. | Time to identified disease progression on SCH 727965 in Part 2 (approx. 6 months) |
Outcome results
None listed