Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas

This is an interventional treatment trial for Large Cell Lymphoma Arising in KSHV-associated Multicentric Castleman Disease focused on measuring HHV8, PEL, Immune Modulation, CC-4047, IMiD Read More

• INCLUSION CRITERIA:

2.1.1.1 KSHV-associated non-Hodgkin lymphoma, with pathology reviewed and confirmed at the NIH. May include WHO recognized tumors

:

2.1.1.1.1 Primary effusion lymphoma (PEL), including extracavitary variant

2.1.1.1.2 Large cell lymphoma arising in the setting of KSHV-associated MCD.

2.1.1.2 Measurable or assessable lymphoma

2.1.1.3 Any HIV status

2.1.1.4 Age 18 years or greater. Because no dosing or adverse event data are currently available on the use of pomalidomide in combination with EPOCH-R in patients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.

2.1.1.5 ECOG performance status 0-4.

2.1.1.6 Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 14 days prior to and again within 24 hours before starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control

2.1.1.7 All study participants must agree to be registered into the mandatory POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program.

2.1.1.8 Able to take aspirin 81mg orally daily or if intolerant of aspirin, able to take a substitute thromboprophylaxis such as low molecular weight heparin.

2.1.1.9 Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

2.1.2.1 Use of other systemic anticancer treatments or agents within the past 2 weeks (4 weeks if the therapy was a monoclonal antibody)

2.1.2.2 Prior dose-adjusted EPOCH or pomalidomide for treatment of KSHV-associated lymphoma

2.1.2.3 Parenchymal brain involvement with lymphoma

2.1.2.4 History of malignant tumors other than KS or KSHV-associated MCD, unless: In complete remission for greater than or equal to 1 year from the time response was first documented or

• Completely resected basal cell carcinoma or
• In situ squamous cell carcinoma of the cervix or anus

2.1.2.5 Inadequate renal function, defined as calculated or estimated creatinine clearance < 60 mL/min unless lymphoma related

2.1.2.6 Inadequate hepatic function:

--2.1.2.6.1 Bilirubin (total) > 1.5 times the upper limit of normal; AST and/or ALT > 3 times the upper limit of normal; EXCEPTIONS:

• Total bilirubin greater than or equal to 5 mg/dL in patients with Gilbert's syndrome as defined by >80% unconjugated
• Total bilirubin greater than or equal to 7.5 with direct fraction > 0.7 if patient is receiving a protease inhibitor at the time of initial evaluation
• Hepatic dysfunction attributed to lymphoma

2.1.2.7 ANC <1000/mm3 and platelets < 75,000/mm3 unless lymphoma, KSHV-MCD, or KICS- related.

2.1.2.8 CTCAEv4.0 Grade 3-4 neuropathy

2.1.2.9 Ejection fraction less than 40% by echocardiography

2.1.2.10 Known drug-related, inherited, or acquired procoagulant disorder including prothrombin gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S deficiency and antiphospholipid syndrome but not including heterozygosity for the Factor V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria for the antiphospholipid syndrome.

2.1.2.11 History of hypersensitivity reactions attributed to thalidomide, lenalidomide, or pomalidomide, including prior development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, or pomalidomide.

2.1.2.12 Breast feeding (if lactating, must agree not to breast feed while taking pomalidomide). Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Pomalidomide, breastfeeding should be discontinued if the mother is treated with Pomalidomide.

2.1.2.13 Uncontrolled severe intercurrent illness including, but not limited to: bacterial, fungal, or life-threatening viral infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements.

2.1.2.14 Any condition, including laboratory abnormalities, which in the opinion of the Principal Investigator or Lead Associate Investigator, would prohibit administration of planned chemotherapeutic intervention, places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study

2.1.2.15 Pregnant women are excluded from this study because pomalidomide is a Category X agent with the potential for teratogenic or abortifacient effects. These potential risks may also apply to other agents used in this study