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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell
• Intervention / Treatment: Drug: SCH 727965; Drug: Bortezomib; Biological: Alemtuzumab

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: March 26, 2009
• First Submitted That Met QC Criteria: March 26, 2009
• First Posted (Estimate): March 30, 2009

Study Record Updates

• Last Update Posted (Estimate): August 7, 2015
• Last Update Submitted That Met QC Criteria: August 6, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma; Leukemia; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Antineoplastic Agents, Immunological; Bortezomib; Alemtuzumab
• Other Study ID Numbers: P04715