This is a phase II study in relapsed/refractory WM patients treated with perifosine. It is designed to assess the proportion of overall confirmed responses (CR + PR + MR) using a two-stage phase II study design to permit early stopping of the trial if there is strong evidence that the study regimen is inactive. In addition, it will assess toxicity of this drug in patients with WM. Patients will receive perifosine 150 mg qhs daily. Patients will be assessed by serum immunoelectrophoresis and IgM level at least every 4 weeks.

This is a phase II study in relapsed/refractory WM patients treated with perifosine. It is designed to assess the proportion of overall confirmed responses (CR + PR + MR) using a two-stage phase II study design to permit early stopping of the trial if there is strong evidence that the study regimen is inactive. In addition, it will assess toxicity of this drug in patients with WM. Patients will receive perifosine 150 mg qhs daily. Patients will be assessed by serum immunoelectrophoresis and IgM level at least every 4 weeks.

Patients will take three 50 mg tablets of perifosine qhs daily (for 28 days cycles) with food. Patients may need anti-emetics and/or anti-diarrheas. All patients should continue therapy unless disease progression is documented on two occasions at least 1 week apart. Patients with progressive disease or who refuse further therapy will be discontinued from the protocol. Dose modifications for toxicity will be performed.

Standard criteria for evaluation of response in WM recommended by the Second International WM Workshop will be used in this study.

Inclusion Criteria:

• Age >= 18 years.
• Must have received prior therapy for their WM and have relapsed or refractory WM. Any number of prior therapies is acceptable.
• Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of > 2 times the upper limit of each institution's normal value is required and over 10% of lymphoplasmacytic cells in the bone marrow.
• ECOG Performance Status (PS) 0, 1, or 2.
• The following laboratory values obtained 14 days prior to registration
• ANC >= 1 x109/L
• PLT >= 75 x109/L
• Total bilirubin ≤ 2.0 mg/dL (If total is elevated check direct and if normal patient is eligible.)
• AST <= 3 x upper limit of normal (ULN)
• Creatinine <= 2 x ULN
• Ability to provide informed consent.
• Life expectancy >= 12 weeks.

Exclusion Criteria:

• Uncontrolled infection.
• Other active malignancies.
• CNS involvement.
• Cytotoxic chemotherapy ≤ 3 weeks, or biologic therapy ≤ 2 weeks, or corticosteroids ≤ 2 weeks, prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than WM such as auto-immune diseases. Plasmapheresis is not considered as an active therapy and can be used at the physician's discretion.
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational.
• Any of the following:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device (IUD), or abstinence, etc.)
• Known to be HIV positive.
• Radiation therapy ≤ 2 weeks prior to registration.