Trial of PD 0332991 Plus Bortezomib in Patients With Relapsed Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) is characterized by cell cycle dysregulation. PD 0332991 is a cyclin-dependent kinase 4 and 6 inhibitor capable of inhibiting cell cycling of MCL. A phase I study has demonstrated the safety and anti-lymphoma activity of PD 0332991. Bortezomib is a first generation proteasome inhibitor approved for treatment of patients with recurrent MCL. Preclinical data suggests that PD 0332991 and bortezomib may act synergistically in MCL.
PD 0332991 will be administered continuously for 12 days followed by a 9 day period without treatment. Bortezomib will be administered by intravenous bolus on days 8, 11, 15, and 18 of each cycle. One cycle is defined as three weeks. A maximum of ten cycles will be administered.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of PD 0332991 Plus Bortezomib in Patients With Relapsed Mantle Cell Lymphoma|
- Determination of maximum tolerated dose (MTD) of PD 0332991 in combination with bortezomib in patients with recurrent mantle cell lymphoma [ Time Frame: Days 1-21 of treatment ] [ Designated as safety issue: Yes ]
MTD will be determined by occurrence of Dose Limiting Toxicities during the first cycle:
- Any treatment-related grade 3 or 4 non-hematologic toxicity (except alopecia)
- Delay in the administration of cycle 2 by more than one week due to treatment-related grade 4 neutropenia or thrombocytopenia or treatment-related grade 3-4 non-hematologic toxicity.
|Study Start Date:||June 2010|
|Estimated Study Completion Date:||November 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: all subjects
Subjects will receive PD 0332991 plus bortezomib. The dose of each agent will be dependent on the time point the subject enters the trial.
Drug: PD 0332991
PD 0332991 will be given on Days 1-12 followed by 9 days of non-treatment in a 21-day cycle. Dose will depend on dose escalation schedule.
(-3a) 50 mg (-3) 50 mg (-2)75 mg (-1)75 mg (1)100 mg (2)125 mg (3)125 mg (3a)100 mg
Other Name: PalbociclibDrug: bortezomib
Given as intravenous bolus on days 8, 11, 15, and 18 of 21-day cycle. Dose depends on dose-escalation schedule.
(-3a)1.0 mg/m2 (-3) 0.7 mg/m2 (-2) 0.7 mg/m2 (-1) 1.0 mg/m2 ( 1) 1.0 mg/m2 ( 2) 1.0 mg/m2 ( 3) 1.3 mg/m2 (3a)1.3 mg/m2
Other Name: Velcade
|Contact: John Leonard, MDfirstname.lastname@example.org|
|Contact: Peter Martin, MDemail@example.com|
|United States, New York|
|Weill Cornell Medical College||Recruiting|
|New York, New York, United States, 10065|
|Contact: Peter Martin, MD firstname.lastname@example.org|
|Principal Investigator: John P Leonard, MD|
|Principal Investigator:||John P Leonard, MD||Weill Medical College of Cornell University|