Back to resultsA Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenström's Macroglobulinemia
Primary Purpose
Waldenström's Macroglobulinemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Perifosine
Sponsored by
About this trial
This is an interventional treatment trial for Waldenström's Macroglobulinemia focused on measuring Waldenström's Macroglobulinemia, Perifosine
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.
Sites / Locations
- Dana-Farber Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Perifosine
Arm Description
Patients will receive perifosine orally at 150 mg daily after food for 28-d cycles.
Outcomes
Primary Outcome Measures
Response rate
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 Outcome Measures
Safety
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
This will be calculated using Kaplan-Meier methodology.
Progression free survival
This will be calculated using Kaplan-Meier methodology.
Duration of response
This will be reported among responding patients.
Full Information
NCT ID
NCT00398710
First Posted
November 9, 2006
Last Updated
March 12, 2018
Sponsor
AEterna Zentaris
Collaborators
Dana-Farber Cancer Institute
1. Study Identification
Unique Protocol Identification Number
NCT00398710
Brief Title
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
2. Study Status
Record Verification Date
November 2011
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
October 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AEterna Zentaris
Collaborators
Dana-Farber Cancer Institute
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenström's Macroglobulinemia
Keywords
Waldenström's Macroglobulinemia, Perifosine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Perifosine
Arm Type
Experimental
Arm Description
Patients will receive perifosine orally at 150 mg daily after food for 28-d cycles.
Intervention Type
Drug
Intervention Name(s)
Perifosine
Other Intervention Name(s)
D-21266, KRX-0401
Intervention Description
150 mg daily (100 mg daily in case of dose reduction)
Primary Outcome Measure Information:
Title
Response rate
Description
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.
Time Frame
Every 4 weeks
Secondary Outcome Measure Information:
Title
Safety
Description
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 Frame
Every 4 weeks
Title
Time to progression
Description
This will be calculated using Kaplan-Meier methodology.
Time Frame
Every 4 weeks
Title
Progression free survival
Description
This will be calculated using Kaplan-Meier methodology.
Time Frame
Every 4 weeks
Title
Duration of response
Description
This will be reported among responding patients.
Time Frame
Every 4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Irene M Ghobrial, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20103671
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.
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A Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenström's Macroglobulinemia
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