Clinical trial NCT00398710: A Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenström's Macroglobulinemia
Official title: A Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenström's Macroglobulinemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Waldenström's Macroglobulinemia
Keywords: Waldenström's Macroglobulinemia
Perifosine
Lead sponsor: AEterna Zentaris
Sponsor class: INDUSTRY
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2006-11-14
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Response rate
timeFrame: Every 4 weeks
Secondary outcomes:
measure: Safety
timeFrame: Every 4 weeks
measure: Time to progression
timeFrame: Every 4 weeks
measure: Progression free survival
timeFrame: Every 4 weeks
measure: Duration of response
timeFrame: Every 4 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Irene M Ghobrial, MD
role: STUDY_CHAIR
References:
citation: Ghobrial IM, Roccaro A, Hong F, Weller E, Rubin N, Leduc R, Rourke M, Chuma S, Sacco A, Jia X, Azab F, Azab AK, Rodig S, Warren D, Harris B, Varticovski L, Sportelli P, Leleu X, Anderson KC, Richardson PG. Clinical and translational studies of a phase II trial of the novel oral Akt inhibitor perifosine in relapsed or relapsed/refractory Waldenstrom's macroglobulinemia. Clin Cancer Res. 2010 Feb 1;16(3):1033-41. doi: 10.1158/1078-0432.CCR-09-1837. Epub 2010 Jan 26.