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

Sponsor

AEterna Zentaris (Industry)

Overall Status

Terminated

CT.gov ID

NCT01002248

Collaborator

Dana-Farber Cancer Institute (Other)

135

Enrollment

Locations

Arms

Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Perifosine Drug: Perifosine Placebo Drug: Bortezomib Drug: Dexamethasone	Phase 3

Detailed Description

A pre-planned interim analysis is expected to take place in Q1 of 2013.

Study Design

Study Type:

Interventional

Actual Enrollment :

135 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Study Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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).	Drug: Perifosine Perifosine will be dosed as one 50 mg pill every day of each cycle. Other Names: D-21266 KRX-0401 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.
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).	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.

Arm

Intervention/Treatment

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).

Drug: Perifosine

Perifosine will be dosed as one 50 mg pill every day of each cycle.

Other Names:

D-21266

KRX-0401

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.

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).

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.

Outcome Measures

Primary Outcome Measures

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 [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.

Secondary Outcome Measures

Overall survival (OS) [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) [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		La Verne	California	United States	91750
2		San Francisco	California	United States	94143
3		San Pablo	California	United States	94806
4		Aurora	Colorado	United States	80012
5		Boulder	Colorado	United States	80303
6		Colorado Springs	Colorado	United States	80909
7		Denver	Colorado	United States	80218
8		Lakewood	Colorado	United States	80228
9		Littleton	Colorado	United States	80120
10		Longmont	Colorado	United States	80501
11		Parker	Colorado	United States	80138
12		Pueblo	Colorado	United States	81008
13		Thornton	Colorado	United States	80260
14		Niles	Illinois	United States	60714
15		Winfield	Illinois	United States	60190
16		Baltimore	Maryland	United States	21201
17		Columbia	Maryland	United States	21044
18	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
19		Morristown	New Jersey	United States	07960
20		Great Neck	New York	United States	11042
21		Fargo	North Dakota	United States	58122
22		Portland	Oregon	United States	97225
23		Tualatin	Oregon	United States	97062
24		Kingsport	Tennessee	United States	37660
25		Bedford	Texas	United States	76022
26		Dallas	Texas	United States	75246
27		Fort Worth	Texas	United States	76104
28		Kerrville	Texas	United States	78028
29		San Antonio	Texas	United States	78217
30		San Antonio	Texas	United States	78229
31		Tyler	Texas	United States	75702
32		Ogden	Utah	United States	84403
33		Christiansburg	Virginia	United States	24073
34		Roanoke	Virginia	United States	24014
35		Salem	Virginia	United States	24153
36		Seattle	Washington	United States	98133
37		Spokane	Washington	United States	99202
38		Vancouver	Washington	United States	98686
39		Milwaukee	Wisconsin	United States	53226
40		Winnipeg	Manitoba	Canada	R3E 0V9
41		Montreal	Quebec	Canada	H1T 2M4
42		Montreal	Quebec	Canada	H3A 1A1
43		Quebec City	Quebec	Canada	G1R 2J6
44		Brno	Czech Republic	Czechia	62500
45		Prague	Czech Republic	Czechia	12821
46		Dublin 24		Ireland
47	Keryx / AOI Pharmaceuticals Investigative Site	Dublin 7		Ireland
48		Dublin 8		Ireland
49		Dublin 9		Ireland
50		Galway		Ireland
51		Limerick		Ireland
52		Sligo		Ireland
53		Tullamore		Ireland
54		Waterford		Ireland
55		Afula		Israel	18101
56		Ashkelon		Israel	78278
57		Beer Sheva		Israel	84101
58		Haifa		Israel	31096
59		Jerusalem		Israel	91031
60		Jerusalem		Israel	91120
61		Nahariya		Israel	22100
62		Petah Tikva		Israel	49100
63		Rehovot		Israel	76100
64		Tel Aviv		Israel	64239
65		Tel-Hashomer		Israel	52621
66		Seoul		Korea, Republic of	110-744
67		Seoul		Korea, Republic of	120-752
68		Seoul		Korea, Republic of	135-710
69		Seoul		Korea, Republic of	137-701
70		Seoul		Korea, Republic of	138-736
71		Moscow		Russian Federation	125284
72		Moscow		Russian Federation	129110
73		Saint Petersburg		Russian Federation	191024
74		Saint Petersburg		Russian Federation	197022
75		Samara		Russian Federation	443095
76		Kosice	Slovak Republic	Slovakia	04166
77		Badalona		Spain	08916
78		Barcelona		Spain	08025
79		Barcelona		Spain	08035
80		Barcelona		Spain	08036
81		La Laguna		Spain	38320
82		Madrid		Spain	28006
83		Madrid		Spain	28034
84		Madrid		Spain	28040
85		Madrid		Spain	28041
86		Pamplona		Spain	31008
87		Valencia		Spain	46026
88		Zaragoza		Spain	50009