Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia
A Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia
Waldenström's Macroglobulinemia (lymphoplasmacytic lymphoma, WM) remains incurable with limited therapeutic options and notably absent FDA approved therapy with any WM indication. Therefore, there is a need to identify new therapeutic agents for WM patients both in the upfront and relapsed/refractory setting. The purpose of this research study is to assess the efficacy of perifosine in patients with relapsed or refractory WM.
Perifosine is a drug that in particular inhibits Akt thought to be important for initiation and progression of malignancies, specifically in lymphomas. In laboratory experiments of WM and lymphoma cell lines, perifosine has shown to have cytotoxic and anti-proliferative activity as a single agent. This drug has been used in clinical research studies of other types of cancers including soft tissue sarcomas, head and neck cancers and prostate cancer. This study uses a two-stage design to evaluate efficacy of perifosine based on overall response (OR). The null and alternative OR rates are 20% and 40%. If 4 or more patients enrolled in the stage one cohort (n=17 patients) achieve OR than accrual will proceed to stage two (n=20 patients). If fewer than 10 ORs are observed then the regimen will be considered ineffective.
Overall Response (OR) Rate
Time to Progression (TTP)
Study Arms / Comparison Groups
Description: Patients receive oral perifosine (150 mg) daily each cycle. Cycle duration is 28 days. After cycle 2, response is assessed and patients with stable or responding disease can continue for another 4 cycles or until disease progression (PD). Protocol treatment duration is 6 cycles but patients may receive perifosine maintenance per investigator discretion in absence of PD.
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Primary Completion Date
Inclusion Criteria: - 18 years of age or older - 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 paraprotein with a minimum IgM level of equal to or greater than 2 times the ULN and over 10% of lymphoplasmacytic cells in bone marrow - ECOG Performance Status 0,1, or 2 - Laboratory values as described in the protocol - Life expectancy of greater than 12 weeks Exclusion Criteria: - Uncontrolled infection - Other active malignancies - CNS involvement - Cytotoxic chemotherapy less than 3 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks prior to registration. - Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational - Pregnant or nursing women - Known to be HIV positive - Radiation therapy less than 2 weeks prior to registration
18 Years - N/A
Accepts Healthy Volunteers
Irene Ghobrial, MD, ,
Dana-Farber Cancer Institute
Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute