A Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenström's Macroglobulinemia - Full Text View

Sponsor:	Keryx / AOI Pharmaceuticals, Inc.
Collaborator:	Dana-Farber Cancer Institute
Information provided by (Responsible Party):	Keryx / AOI Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00398710

Purpose

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.

Condition	Intervention	Phase
Waldenström's Macroglobulinemia	Drug: Perifosine	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenström's Macroglobulinemia

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer

Drug Information available for: Perifosine

U.S. FDA Resources

Further study details as provided by Keryx / AOI Pharmaceuticals, Inc.:

Primary Outcome Measures:

Response rate [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicities [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
Time to progression [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
Progression free survival [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
Duration of response [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]

Enrollment:	37
Study Start Date:	October 2006
Study Completion Date:	October 2011
Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Intervention Details:

100 - 150 mg daily

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00398710

Locations

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Keryx / AOI Pharmaceuticals, Inc.

Dana-Farber Cancer Institute

Investigators

Study Chair:

Irene M Ghobrial, MD

Dana-Farber Cancer Institute

More Information

Publications:

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. Epub 2010 Jan 26.

Responsible Party:	Keryx / AOI Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00398710 History of Changes
Other Study ID Numbers:	Perifosine 221
Study First Received:	November 9, 2006
Last Updated:	November 10, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Keryx / AOI Pharmaceuticals, Inc.:

Waldenström's Macroglobulinemia
Perifosine

Additional relevant MeSH terms:

Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias

Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on February 12, 2012