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Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia

Primary Purpose

Waldenstrom's Macroglobulinemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Perifosine
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Waldenstrom's Macroglobulinemia focused on measuring relapsed Waldenstrom's Macroglobulinemia, refractory Waldenstrom's Macroglobulinemia, WM, perifosine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Perifosine

Arm Description

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.

Outcomes

Primary Outcome Measures

Overall Response (OR) Rate
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.

Secondary Outcome Measures

Time to Progression (TTP)
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.
Progression Free Survival (PFS)
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.
Treatment-Related Grade 3-4 Adverse Event Rate
The percentage of patients experiencing treatment-related grade 3-4 adverse events based on CTCAEv3 as reported on case report forms.

Full Information

First Posted
January 12, 2007
Last Updated
November 21, 2017
Sponsor
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00422656
Brief Title
Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia
Official Title
A Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenstrom's Macroglobulinemia
Keywords
relapsed Waldenstrom's Macroglobulinemia, refractory Waldenstrom's Macroglobulinemia, WM, 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 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.
Intervention Type
Drug
Intervention Name(s)
Perifosine
Other Intervention Name(s)
KRX-0401
Primary Outcome Measure Information:
Title
Overall Response (OR) Rate
Description
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.
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+).
Secondary Outcome Measure Information:
Title
Time to Progression (TTP)
Description
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.
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.
Title
Progression Free Survival (PFS)
Description
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.
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.
Title
Treatment-Related Grade 3-4 Adverse Event Rate
Description
The percentage of patients experiencing treatment-related grade 3-4 adverse events based on CTCAEv3 as reported on case report forms.
Time Frame
Adverse events were collected every cycle on treatment.The median treatment duration was 5.6 months (range, 1.8-21.5+).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Irene Ghobrial, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
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.
Results Reference
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Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia

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