Clinical trial NCT00415064: Phase I Study of Perifosine + Lenalidomide and Dexamethasone for Patients With Multiple Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Perifosine
Lenalidomide
Dexamethasone
Lead sponsor: AEterna Zentaris
Sponsor class: INDUSTRY
First posted: 2006-12-22
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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:

1. Perifosine 50 mg, lenalidomide 15 mg and dexamethasone 20 mg
2. Perifosine 50 mg, lenalidomide 25 mg and dexamethasone 20 mg
3. Perifosine 100 mg, lenalidomide 15 mg and dexamethasone 20 mg
4. 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.

Eligibility criteria: Inclusion Criteria:

* Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria, as follows.
* Major criteria:

  1. Plasmacytomas on tissue biopsy.
  2. Bone marrow plasmacytosis (\> 30% plasma cells).
  3. 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

Primary outcomes:
measure: Adverse Events
timeFrame: Every cycle
Secondary outcomes:
measure: Clinically significant changes in the patient's physical examination, vital signs, and clinical laboratory results
timeFrame: Every 12 weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
state: Michigan
Study officials:
affiliation: University of Michigan
name: Andrzej J Jakubowiak, MD, PhD
role: STUDY_CHAIR
References:
citation: Jakubowiak AJ, Richardson PG, Zimmerman T, Alsina M, Kaufman JL, Kandarpa M, Kraftson S, Ross CW, Harvey C, Hideshima T, Sportelli P, Poradosu E, Gardner L, Giusti K, Anderson KC. Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study. Br J Haematol. 2012 Aug;158(4):472-80. doi: 10.1111/j.1365-2141.2012.09173.x. Epub 2012 May 29.