Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia

November 21, 2017 updated by: Irene Ghobrial, MD, Dana-Farber Cancer Institute

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Perifosine
Other Names:
  • KRX-0401

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response (OR) Rate
Time Frame: Disease was assessed every cycle for the first 12 months and every 3 months thereafter. The median duration of treatment with perifosine was 5.6 months (range, 1.8- 21.5+).
OR rate is the percentage of patients achieving Complete Response (CR), Partial Response (PR) or Minimal Response (MR) during treatment based on criteria from the 2nd International Workshop on WM. (Weber D, Treon S, et al. Seminars in Oncology 2003). CR: Disappearance of serum monoclonal IgM protein (IgM M-protein) by immunofixation; no histologic evidence of bone marrow (BM) involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan); PR: At least 50% reduction of IgM M-protein and at least 50% decrease in adenopathy/organomegaly on physical examination or on CT scan; and MR: At least 25% but less than 50% reduction of IgM M-protein by protein electrophoresis. Patients must have no new symptoms or signs of active disease.
Disease was assessed every cycle for the first 12 months and every 3 months thereafter. The median duration of treatment with perifosine was 5.6 months (range, 1.8- 21.5+).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Progression (TTP)
Time Frame: Disease was assessed every cycle for the first 12 months and every 3 months thereafter. Median follow-up time was 19.5 months and range up to 24 months.
TTP estimated using the Kaplan-Meier method is defined as the time from registration to disease progression (PD) based on criteria from the 2nd International Workshop on WM. (Weber D, Treon S, et al. Seminars in Oncology 2003) Patients without PD are censored at time of last disease assessment. PD: At least 25% increase in serum monoclonal IgM protein by electrophoresis confirmed with a second measurement at least 2 weeks apart, or progression of clinically significant findings due to disease (i.e., anemia, thrombocytopenia, leucopenia, bulky adenopathy/organomegaly) or symptoms (unexplained recurrent fever of at least 38.4oC, drenching night sweats, at least 10% body weight less, or hyperviscosity, neuropathy, symptomatic cryoglobulinemia, or amyloidosis) attributable to WM.
Disease was assessed every cycle for the first 12 months and every 3 months thereafter. Median follow-up time was 19.5 months and range up to 24 months.
Progression Free Survival (PFS)
Time Frame: Disease was assessed every cycle for the first 12 months and every 3 months thereafter. Median follow-up time was 19.5 months and range up to 24 months.
PFS estimated using the Kaplan-Meier method is defined as the time from registration to death from any cause or disease progression (PD) based on criteria from the 2nd International Workshop on WM. (Weber D, Treon S, et al. Seminars in Oncology 2003) Patients alive without PD are censored at time of last disease assessment. PD: At least 25% increase in serum monoclonal IgM protein by electrophoresis confirmed with a second measurement at least 2 weeks apart, or progression of clinically significant findings due to disease (i.e., anemia, thrombocytopenia, leucopenia, bulky adenopathy/organomegaly) or symptoms (unexplained recurrent fever of at least 38.4oC, drenching night sweats, at least 10% body weight less, or hyperviscosity, neuropathy, symptomatic cryoglobulinemia, or amyloidosis) attributable to WM.
Disease was assessed every cycle for the first 12 months and every 3 months thereafter. Median follow-up time was 19.5 months and range up to 24 months.
Treatment-Related Grade 3-4 Adverse Event Rate
Time Frame: Adverse events were collected every cycle on treatment.The median treatment duration was 5.6 months (range, 1.8-21.5+).
The percentage of patients experiencing treatment-related grade 3-4 adverse events based on CTCAEv3 as reported on case report forms.
Adverse events were collected every cycle on treatment.The median treatment duration was 5.6 months (range, 1.8-21.5+).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Investigators

  • Principal Investigator: Irene Ghobrial, MD, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

January 12, 2007

First Submitted That Met QC Criteria

January 12, 2007

First Posted (Estimate)

January 17, 2007

Study Record Updates

Last Update Posted (Actual)

December 26, 2017

Last Update Submitted That Met QC Criteria

November 21, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-077

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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