Study of Pomalidomide for Treatment of Relapsed/Refractory Primary Central Nervous System Lymphoma and Newly Diagnosed or Relapsed/Refractory Intraocular Lymphoma
This phase I clinical trial aims to elucidate the maximal tolerated dose and side effects of pomalidomide in patients with relapsed or refractory primary central nervous system lymphoma or newly diagnosed or relapsed or refractory vitreoretinal lymphoma (Intraocular lymphoma). The study will also determine the efficacy and survival related to pomalidomide therapy in a MTD expanded cohort.
Rationale - Pomalidomide is a novel immunomodulatory agent, which has shown significant activity against CNS lymphoma in preclinical studies. Blood brain barrier is an obstacle in treatment of brain tumors such as CNS lymphoma. Pomalidomide was shown to have an excellent CNS penetration in a murine model: approximately 39% of systemically administered pomalidomide could penetrate the central nervous system. As such, pomalidomide is a promising immunomodulator to be tested in a clinical trial for CNS lymphoma. It works by killing the lymphoma cells directly as well as indirectly via activation of the immune response against lymphoma cells.
Primary Central Nervous System Lymphoma
Primary Vitreoretinal Lymphoma (Intraocular Lymphoma)
|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 Patients With Newly Diagnosed or Relapsed/Refractory Primary Vitreoretinal Lymphoma|
- Maximum tolerated dose (MTD) of pomalidomide as 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 ]MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).
- Progression-free survival [ Time Frame: Time from registration to progression or death due to PCNSL or PVRL lymphoma, assessed up to 1 year ] [ 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 1 year ] [ Designated as safety issue: No ]The distribution of overall survival will be estimated using the method of Kaplan-Meier.
- Overall response rate [ Time Frame: upto one year ] [ Designated as safety issue: No ]The overall response rate will be estimated by the number of patients with an objective status of complete response (CR), unconfirmed complete response (CRu), or partial response (PR) divided by the total number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (pomalidomide, dexamethasone)
In phase I, dose-escalation study of pomalidomide will be performed to determine the maximal tolerated dose (MTD). The dose escalation schedule consists of different dose levels: 2 mg/day (level -1), 3 mg/day (level 1, starting dose level), 5 mg/day (level 2), 7 mg/day (level 3), 10 mg/day (level 4). Dose escalation is to be determined by dose limiting toxicity (DLT). In the MTD expanded cohort, the maximal tolerated dose of pomalidomide as determined by phase I will be used.
Patients receive pomalidomide orally (PO) on days 1-21 of each 28-day cycle. In the first and second cycles of treatment, pomalidomide is given with dexamethasone 40 mg PO on days 1, 8, 15, and 22. Pomalidomide alone is given after the second cycle of treatment. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Name: CC-4047Drug: dexamethasone
I. To establish the maximum tolerated dose (MTD) of pomalidomide in patients with CNS lymphoma.
I. To evaluate the efficacy (overall response rate) and safety of pomalidomide in patients with primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL) in an MTD expanded cohort.
II. To evaluate overall survival and progression free survival.
Objectives of correlative research:
I. To study the pharmacokinetics of pomalidomide in the central nervous system.
II. To identify the predictive biomarkers for responsiveness to pomalidomide.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01722305
|United States, Arizona|
|Mayo Clinic Campus in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Mayo Clinic Campus in Florida|
|Jacksonville, Florida, United States, 32224|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Han W. Tun, M.D.||Mayo Clinic in Florida|