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:||Intervention Model: Single Group Assignment
Masking: None (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 ]
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 2017|
|Primary Completion Date:||June 15, 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
Escalating doses of PD 0332991 in combination with bortezomib will be studied sequentially, with at least 3 patients in each dose level until the MTD is determined. PD 0332991 will be given orally, starting on Day 1 of each cycle, once a day for 12 days followed by 9 days without treatment. Bortezomib will be given by intravenous (IV) bolus or subcutaneously (taking 3 to 5 seconds to administer) on days 8, 11, 15 and 18. For dose levels 3a and 4b, bortezomib will be administered only on days 15 and 18. One cycle is defined as 3 weeks (21 days). Subjects will remain on treatment until they meet criteria for withdrawal from treatment described in section 5.4 (e.g., DLT, disease progression, unacceptable toxicity, or withdrawal of consent).
The pharmacist will maintain records of drug receipt (if applicable), drug preparation, and dispensing, including the applicable lot numbers, patients' height, body weight, and body surface area, and total drug administered in milliliters and milligrams. Any discrepancy between the calculated dose and dose administered and the reason for the discrepancy must be recorded in the source documents.
Treatment will be administered only to eligible patients under the supervision of the investigator or identified sub-investigator (s). Treatment will be administered on an outpatient basis. Reported adverse events and potential risks are described in Section 7. Appropriate dose modifications are described in Section 6. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's malignancy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01111188
|United States, New York|
|Weill Cornell Medical College|
|New York, New York, United States, 10065|
|Principal Investigator:||John P Leonard, MD||Weill Medical College of Cornell University|