Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma
Central Nervous System Non-Hodgkin Lymphoma
Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System
Recurrent Adult Diffuse Large Cell Lymphoma
Other: Pharmacological Study
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Pomalidomide for Patients With Relapsed/Refractory Primary CNS Lymphoma and Primary Vitreoretinal Lymphoma|
- MTD of pomalidomide when given in combination with dexamethasone determined by dose-limiting toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]The number and severity of all adverse events will be tabulated and summarized in this patient population both overall and by dose level. The grade 3+ adverse events will also be described and summarized in a similar fashion. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
- Overall response rate defined as number of patients with an objective status of complete response (CR), complete response/unconfirmed (Cru), or partial response (PR) divided by total number of evaluable patients [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
- Progression-free survival [ Time Frame: Time from registration to progression or death due to PCNSL or PVRL lymphoma, assessed up to 2 years ] [ Designated as safety issue: No ]The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
- Overall survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]The distribution of overall survival will be estimated using the method of Kaplan-Meier.
- Incidence of adverse events, graded according to CTCAE 4.0 [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.
- Pharmacokinetics of pomalidomide in the CNS [ Time Frame: Up to day 22 of course 1 ] [ Designated as safety issue: No ]Based on pomalidomide levels in blood and CSF at different time points, area under curve will be determined.
- Predictive biomarkers for response to pomalidomide [ Time Frame: Up to day 21 of course 1 ] [ Designated as safety issue: No ]Correlation studies will be performed to identify predictive immune markers for response to pomalidomide. Immune cell counts and cytokine profile will be evaluated in blood and CSF at day 1 and day 21 of course 1. Values at each time point and changes after pomalidomide treatment will be both graphically and quantitatively summarized and explored. Wilcoxon rank sum test and Fisher's exact test will be utilized where appropriate to assess the relationships of these markers with response.
|Study Start Date:||April 2013|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (pomalidomide, dexamethasone)
Patients receive pomalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 of courses 1 and 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: Dexamethasone
Other Name: DMOther: Pharmacological Study
Optional correlative studies
Other Name: pharmacological studiesOther: Laboratory Biomarker Analysis
Optional correlative studies
I. To establish the maximum tolerated dose (MTD) of pomalidomide in combination with dexamethasone in patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL).
I. To evaluate the efficacy (overall response rate) and safety of pomalidomide in combination with dexamethasone in patients with PCNSL and PVRL lymphoma in an MTD expanded cohort.
II. To evaluate overall survival and progression free survival.
I. To study the pharmacokinetics of pomalidomide in the central nervous system. II. To identify the predictive biomarkers for responsiveness to pomalidomide.
OUTLINE: This is a dose-escalation study of pomalidomide.
Patients receive pomalidomide orally (PO) on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 of courses 1 and 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01722305
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Massachusetts|
|Dana-Farber Harvard Cancer Center|
|Boston, Massachusetts, United States, 02115|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Virginia|
|University of Virginia|
|Charlottesville, Virginia, United States, 22908|
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Han Tun||Mayo Clinic in Florida|