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

Recurrent Adult Diffuse Large Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01722305
• Other study ID #: MC1281
• Secondary ID: NCI-2012-01948MC
• Status: Completed
• Phase: Phase 1
• Start date: April 8, 2013
• Est. completion date: July 15, 2019

Study information

• Verified date: July 2019
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 15, 2019
• Est. primary completion date: June 3, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Relapsed or refractory primary central nervous system (CNS) diffuse large B cell lymphoma (PCNSDLBCL) with a CNS lesion, with cerebrospinal fluid (CSF) relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy; NOTE: tissue biopsy is not absolutely necessary for CNS tumor unless clinical and radiologic findings strongly suggest other etiologies as per treating physician; initial diagnosis must be made by tissue biopsy; NOTE: patients with B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma are also eligible for the protocol as long as they meet other criteria; patients with typical Burkitt lymphoma are not eligible

• Relapsed/refractory primary vitreoretinal diffuse large B cell lymphoma (DLBCL) with a CNS lesion, with CSF relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy; NOTE: tissue biopsy requirement of the CNS lesion is as outlined in bullet above

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3

• Absolute neutrophil count (ANC) >= 1000/uL

• Platelets (PLT) >= 100,000/uL

• Total bilirubin =< 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN the direct bilirubin must be =< 1.5 x ULN (=< 0.45 mg/dL)

• Aspartate aminotransferase (AST) =< 3 x ULN

• Creatinine =< 2.5 x ULN

• Females of reproductive potential must be willing to adhere to the scheduled pregnancy testing as required in the POMALYST REMS (TM) program

• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or heparin)

• Provide informed written consent

• Willing to return to participating medical institutions for follow-up

• Willing to provide tissue samples for correlative research purposes

• Willing to be registered into the mandatory POMALYST REMS (TM) program, and willing and able to comply with the requirements of the POMALYST REMS (TM) program

Exclusion Criteria:

• Any of the following

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs

• Uncontrolled infection

• Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration; NOTE: patients who have recovered from cytopenia related to previous treatment and meet criteria of this protocol will be eligible

• Persistent toxicities >= grade 3 from prior chemotherapy or biological therapy regardless of interval since last treatment

• History of thromboembolic episodes =< 3 months prior to registration

• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)

• Immunodeficiency states including human immunodeficiency virus (HIV) infection

• Active hepatitis B or C with uncontrolled disease; NOTE: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B core immunoglobulin M antibody (HBcIgM Ab), hepatitis B surface antigen (HBsAg) and hepatitis C antibody screen (HCV Ab Scrn) w/reflex testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior hepatitis B (HBV) infection

• Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment

• Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications

• Any severe and/or uncontrolled medical conditions or other conditions that, in the treating physician's opinion, could adversely impact their ability to participate in the study

• Major surgery =< 4 weeks prior to registration or have not recovered from side effects of such therapy

• New York Heart Association classification III or IV

Related Conditions & MeSH terms

• B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma
• Burkitt Lymphoma
• Central Nervous System Lymphoma
• Intraocular Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System
• Recurrent Adult Diffuse Large Cell Lymphoma
• Retinal Lymphoma

Intervention

Drug:
• Dexamethasone
Given PO

Other:
• Laboratory Biomarker Analysis
Optional correlative studies
• Pharmacological Study
Optional correlative studies

Drug:
• Pomalidomide
Given PO

Locations

Country	Name	City	State
United States	Dana-Farber Harvard Cancer Center	Boston	Massachusetts
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetics of pomalidomide in the CNS	Based on pomalidomide levels in blood and CSF at different time points, area under curve will be determined.	Up to day 22 of course 1
Other	Predictive biomarkers for response to pomalidomide	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.	Up to day 21 of course 1
Primary	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	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.	28 days
Secondary	Incidence of adverse events, graded according to CTCAE 4.0	The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.	Up to 30 days post-treatment
Secondary	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	Exact binomial 95% confidence intervals for the true overall response rate will be calculated.	Up to 2 years
Secondary	Overall survival time	The distribution of overall survival will be estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 2 years
Secondary	Progression-free survival	The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.	Time from registration to progression or death due to PCNSL or PVRL lymphoma, assessed up to 2 years