Phase I Study of Perifosine + Lenalidomide and Dexamethasone for Patients With Multiple Myeloma

Study Overview
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Brief Summary
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This is a phase I study of perifosine in combination with lenalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma. The current protocol will enroll patients with relapsed or refractory multiple myeloma requiring second or third line therapy. Six patients each will be treated with at one of 4 dose levels in a phase 1 study. All patients will receive perifosine, lenalidomide and dexamethasone of each 28 day cycle. The doses of perifosine and lenalidomide will be varied in each group. The dose of dexamethasone will remain constant.

Detailed Description
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This is a phase I study of perifosine in combination with lenalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma. All patients will receive lenalidomide daily for days 1 to 21 of each 28 day cycle. Perifosine will be given daily qhs with food. Dexamethasone will be given on days 1-4, 9-12 and 17-20 for 4 cycles. After 4 cycles dexamethasone will be given only on days 1-4. Four dose levels will be studied: Perifosine 50 mg, lenalidomide 15 mg and dexamethasone 20 mg Perifosine 50 mg, lenalidomide 25 mg and dexamethasone 20 mg Perifosine 100 mg, lenalidomide 15 mg and dexamethasone 20 mg Perifosine 100 mg, lenalidomide 25 mg and dexamethasone 20 mg Six patients will be enrolled at each dose level until the maximum tolerated dose (MTD) is reached. Six additional patients will be treated at the MTD.

Official Title
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An Open-Label Phase I Study of the Safety of Perifosine in Combination With Lenalidomide and Dexamethasone for Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Perifosine
* Drug: Lenalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria, as follows. Major criteria: Plasmacytomas on tissue biopsy. Bone marrow plasmacytosis (> 30% plasma cells). Monoclonal immunoglobulin spike on serum electrophoresis immunoglobulin G (IgG) >3.5 g/dL or immunoglobulin A (IgA) > 2.0 g/dL; kappa or lambda light chain excretion > 1 g/day on 24 hour urine protein electrophoresis. Patients must have relapsed or refractory disease (refractory is defined as progression during treatment or within 60 days after the completion of treatment) requiring 2nd or 3rd line therapy Patients refractory to a combination of lenalidomide and dexamethasone will not be eligible. Patients may have received lenalidomide and/or dexamethasone Exclusion Criteria: Renal insufficiency (serum creatinine levels > 3 mg/dL).. History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine). Known hypersensitivity to thalidomide

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Perifosine|Perifosine given in either 50 mg or 100 mg / day|
|Drug: Lenalidomide|Lenalidomide given in either 15 or 25 mg / day|
|Drug: Dexamethasone|Dexamethasone given in 20 mg / day|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  | Every cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically significant changes in the patient's physical examination, vital signs, and clinical laboratory results |  | Every 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Perifosine, Lenalidomide, Dexamethasone