Waldenström's Macroglobulinemia
Conditions
Keywords
Waldenström's Macroglobulinemia, Perifosine
Brief summary
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.
Detailed description
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.
Interventions
DRUGPerifosine
150 mg daily (100 mg daily in case of dose reduction)
Sponsors
Dana-Farber Cancer Institute
AEterna Zentaris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate | Every 4 weeks | Response will include complete remission, partial remission (PR), and minimal response (MR) using serum protein electrophoresis. Response will also be assessed by IgM using nephelometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety | Every 4 weeks | Adverse events will be assessed at each visit and graded according to the National Cancer Institute Common Toxicity Criteria (version 3.0) from the first dose until 30 d after the last dose of perifosine. |
| Time to progression | Every 4 weeks | This will be calculated using Kaplan-Meier methodology. |
| Progression free survival | Every 4 weeks | This will be calculated using Kaplan-Meier methodology. |
| Duration of response | Every 4 weeks | This will be reported among responding patients. |
Countries
United States
Outcome results
None listed