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

• ClinicalTrials.gov Identifier: NCT01002248
• Recruitment Status: Terminated
• First Posted: October 27, 2009
• Last Update Posted: February 9, 2018
• Sponsor: AEterna Zentaris
• Collaborator: Dana-Farber Cancer Institute
• Information provided by (Responsible Party): AEterna Zentaris

Tracking Information

• First Submitted Date: October 23, 2009
• First Posted Date: October 27, 2009
• Last Update Posted Date: February 9, 2018
• Study Start Date: December 2009
• Actual Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: October 26, 2009): Progression-free survival [ Time Frame: q 3 weeks ]

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Assessment of Efficacy and Safety of Perifosine, Bortezomib and Dexamethasone in Multiple Myeloma Patients
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• 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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 20, 2013): 135
• Original Estimated Enrollment (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

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: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, Ireland, Israel, Korea, Republic of, Russian Federation, Slovakia, Spain, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01002248
• Other Study ID Numbers: 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: AEterna Zentaris
• Collaborators: Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Paul Richardson, MD; Dana-Farber Cancer Institute

• PRS Account: AEterna Zentaris
• Verification Date: March 2013