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