Clinical Trial: Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: Phase I Trial of Pomalidomide for Patients With Relapsed/Refractory Primary CNS Lymphoma and Primary Vitreoretinal Lymphoma

Brief Summary: This phase I trial studies the side effects and best dose of pomalidomide when given together with dexamethasone in treating patients with primary central nervous system lymphoma that has come back (relapsed) or does not respond to treatment (refractory) or intraocular lymphoma that is newly diagnosed, relapsed or refractory. Pomalidomide may stimulate the immune system to kill cancer cells. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping them from spreading. Giving pomalidomide together with dexamethasone may kill more cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.


Sponsor: Mayo Clinic

Current Primary Outcome: 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) version 4.0 [ Time Frame: 28 days ]

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.


Original Primary Outcome: 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 ]

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).


Current Secondary Outcome:

  • Incidence of adverse events, graded according to CTCAE 4.0 [ Time Frame: Up to 30 days post-treatment ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.
  • 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 ]
    Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
  • Overall survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 2 years ]
    The distribution of overall survival will be estimated using the method of Kaplan-Meier.
  • Progression-free survival [ Time Frame: Time from registration to progression or death due to PCNSL or PVRL lymphoma, assessed up to 2 years ]
    The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.


Original Secondary Outcome:

  • Progression-free survival [ Time Frame: Time from registration to progression or death due to PCNSL or PVRL lymphoma, assessed up to 1 year ]
    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 ]
    The distribution of overall survival will be estimated using the method of Kaplan-Meier.
  • Overall response rate [ Time Frame: upto one year ]
    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.


Information By: Mayo Clinic

Dates:
Date Received: November 2, 2012
Date Started: April 2013
Date Completion: June 2017
Last Updated: March 1, 2017
Last Verified: November 2016