Assessment of Efficacy and Safety of Perifosine, Bortezomib and Dexamethasone in Multiple Myeloma Patients

Tracking Information
First Submitted Date ICMJE	October 23, 2009
First Posted Date ICMJE	October 27, 2009
Last Update Posted Date	February 9, 2018
Study Start Date ICMJE	December 2009
Actual Primary Completion Date	March 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 6, 2018)	Determine the PFS (progression free survival) in patients with multiple myeloma, treated with perifosine, bortezomib and dexamethasone compared to patients treated with placebo, bortezomib and dexamethasone [ Time Frame: 6 - 24 months ]; Progression-free survival will be defined as the time between randomization and the date of progression that occurred during the Core Phase.
Original Primary Outcome Measures ICMJE; (submitted: October 26, 2009)	Progression-free survival [ Time Frame: q 3 weeks ]
Change History	Complete list of historical versions of study NCT01002248 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 6, 2018)	Overall survival (OS) [ Time Frame: Up to 24 months ]OS is defined as time from randomization to death from any cause during the Core Phase of the study.; Overall response rate (ORR) [ Time Frame: 6 - 24 months ]The ORR for each treatment arm will be estimated as the proportion of responders, defined as a patient whose best overall response is PR or better during the treatment period, using criteria prospectively established.; Adverse Events [ Time Frame: Up to 24 months ]Each AE and SAE term submitted will be mapped to a preferred term (PT) using the MedDRA dictionary. The investigator will classify the severity of AEs using the NCI CTCAE v3.0 and will assess the relationship of each event to each study treatment.
Original Secondary Outcome Measures ICMJE; (submitted: October 26, 2009)	Overall survival [ Time Frame: q 3 weeks ]; Overall response rate [ Time Frame: q 3 weeks ]; Adverse Events [ Time Frame: q 3 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Assessment of Efficacy and Safety of Perifosine, Bortezomib and Dexamethasone in Multiple Myeloma Patients
Official Title ICMJE	A Phase III Randomized Study to Assess the Efficacy and Safety of Perifosine Added to the Combination of Bortezomib and Dexamethasone in Multiple Myeloma Patients
Brief Summary	This is a randomized Phase III study to evaluate the efficacy and safety of perifosine when added to the combination of bortezomib and dexamethasone in multiple myeloma patients who have relapsed on a prior bortezomib treatment regimen.
Detailed Description	A pre-planned interim analysis is expected to take place in Q1 of 2013.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Multiple Myeloma
Intervention ICMJE	Drug: Perifosine Perifosine will be dosed as one 50 mg pill every day of each cycle. Other Names: D-21266 KRX-0401; Drug: Perifosine Placebo Perifosine placebo will be dosed as one 50 mg pill every day of each cycle.; Drug: Bortezomib Bortezomib will be dosed at 1.3 mg/m2 on Days 1, 4, 8, and 11 every 21 days.; Drug: Dexamethasone Dexamethasone will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.
Study Arms	Experimental: Perifosine added to combination Perifosine added to the combination of Bortezomib and Dexamethasone. Perifosine is is supplied as a film-coated tablet containing 50 mg of active ingredient. Perifosine will be administered orally on an outpatient basis throughout the study. Daily administration will be one 50 mg tablet. The first dose of perifosine should be taken on the same day that bortezomib and dexamethasone are administered (Cycle 1 Day 1). Interventions: Drug: Perifosine Drug: Bortezomib Drug: Dexamethasone; Placebo Comparator: Perifosine Placebo added to combination Perifosine placebo added to the combination of Bortezomib and Dexamethasone. The placebo for perifosine is provided in 256 mg white to off-white, round, biconvex film-coated tablets to permit a blinded trial with perifosine 50 mg film coated tablets. Placebo will be administered orally on an outpatient basis throughout the study. Daily administration will be one perifosine placebo tablet. The first dose of placebo should be taken on the same day that bortezomib and dexamethasone are administered (Cycle 1 Day 1). Interventions: Drug: Perifosine Placebo Drug: Bortezomib Drug: Dexamethasone
Publications *	Richardson PG, Nagler A, Ben-Yehuda D, Badros A, Hari P, Hajek R, Spicka I, Kaya H, Le Blanc R, Yoon SS, Kim K, Martinez-Lopez J, Mittelman M, Shpilberg O, Tothova E, Laubach JP, Ghobria IM, Leiba M, Gatt ME, Sportelli P, Chen M, Anderson KC. Randomized Placebo-Controlled Phase III Study Of Perifosine Combined With Bortezomib and Dexamethasone In Relapsed, Refractory Multiple Myeloma Patients Previously Treated With Bortezomib. Blood 2013 ASH Meeting Proceedings;122:abstract 3189
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: March 20, 2013)	135
Original Estimated Enrollment ICMJE; (submitted: October 26, 2009)	300
Actual Study Completion Date	March 2013
Actual Primary Completion Date	March 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patient was previously diagnosed with multiple myeloma based on standard diagnostic criteria.; Patients must have relapsed (progressed > 60 days) after their last dose of bortezomib-based therapy. In addition, patients may be relapsed or refractory to other non-bortezomib-based therapies.; Patient has received at least 1 but not more than 4 prior anti-myeloma regimens and has progressive disease after the most recent treatment regimen.; Patients must have adequate organ and marrow function. Exclusion Criteria: Patients must not be refractory to any bortezomib-containing regimen.; History of allergic reactions or intolerance attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine), bortezomib or dexamethasone or any of their components.; Prior treatment with perifosine or an investigational proteasome inhibitor.; Chemotherapy or other therapy experimental or proven that is or may be active against myeloma within two weeks (14 days) prior to Cycle 1 Day 1.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada, Czechia, Ireland, Israel, Korea, Republic of, Russian Federation, Slovakia, Spain, United States
Removed Location Countries	Czech Republic
Administrative Information
NCT Number ICMJE	NCT01002248
Other Study ID Numbers ICMJE	Perifosine 339
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	AEterna Zentaris
Study Sponsor ICMJE	AEterna Zentaris
Collaborators ICMJE	Dana-Farber Cancer Institute
Investigators ICMJE	Principal Investigator: Paul Richardson, MD Dana-Farber Cancer Institute
PRS Account	AEterna Zentaris
Verification Date	March 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP