SCH 727965 in Patients With Mantle Cell Lymphoma or B-Cell Chronic Lymphocytic Leukemia (Study P04715)

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Phase 2 Study of SCH 727965 in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (MCL) or B-Cell Chronic Lymphocytic Leukemia (B-CLL)

Conditions
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Lymphoma, Mantle-Cell, Leukemia, Lymphocytic, Chronic, B-Cell

Intervention / Treatment
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* Drug: SCH 727965
* Drug: Bortezomib
* Biological: Alemtuzumab


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 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.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with MCL randomized to SCH 727965<br> | Drug: SCH 727965<br>* SCH 727965 50 mg/m2 IV on Day 1 of each 21-day cycle until disease progression.<br>|
| Active Comparator: Participants with MCL randomized to bortezomib<br> | Drug: Bortezomib<br>* Bortezomib 1.3 mg/m2 IV on Days 1, 4, 8, and 11 of each 21-day cycle until disease progression.<br>* Other names: Velcade;|
| Experimental: MCL treated w/SCH 727965 after progression on bortezomib<br> | Drug: SCH 727965<br>* SCH 727965 50 mg/m2 IV on Day 1 of each 21-day cycle until disease progression.<br>|
| Experimental: Participants with B-CLL randomized to SCH 727965<br> | Drug: SCH 727965<br>* SCH 727965 50 mg/m2 IV on Day 1 of each 21-day cycle until disease progression.<br>|
| Active Comparator: Participants with B-CLL randomized to alemtuzumab<br> | Biological: Alemtuzumab<br>* 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.<br>* Other names: Campath;|
| Experimental: B-CLL treated w/ SCH 727965 after progression on alemtuzumab<br> | Drug: SCH 727965<br>* SCH 727965 50 mg/m2 IV on Day 1 of each 21-day cycle until disease progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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) |