Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia

NCT ID: NCT00422656

Last Updated: 2017-12-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2012-11-30

Brief Summary

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.

Detailed Description

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.

Conditions

Waldenstrom's Macroglobulinemia

Keywords

relapsed Waldenstrom's Macroglobulinemia; refractory Waldenstrom's Macroglobulinemia; WM; perifosine

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Perifosine

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.

Group Type: EXPERIMENTAL

Perifosine

Intervention Type: DRUG

Interventions

Perifosine

Intervention Type: DRUG

Other Intervention Names

KRX-0401

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Irene Ghobrial, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Irene Ghobrial, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20103671 (View on PubMed)

Other Identifiers

06-077

Identifier Type: -

Identifier Source: org_study_id