Phase III Intergroup Study of Lenalidomide (CC-5013) Versus Placebo Maintenance Therapy Following Single Autologous
Stem Cell Transplant for Multiple Myeloma (CALGB 100104): Initial Report of Patient Accrual and Adverse Events
Philip L. McCarthy, MD; Kouros Owzar, PhD; Craig Hofmeister, MD; Hani Hassoun, MD; David D Hurd, MD; Edward A. Stadtmauer, MD; Sergio Giralt, MD; Paul Richardson, MD, PhD; Daniel J.
Weisdorf, MD; Marcelo C. Pasquini, MD; Vera Hars, MS; Michael Kelly, MA; John Postiglione BA, Susan Sutherland BS, Kenneth C. Anderson, MD; Charles Linker, MD for the Cancer and Leukemia
Group B (CALGB), Eastern Cooperative Oncology Group (ECOG) and Blood and Marrow Transplant Clinical Trials Network (BMT-CTN)
Introduction
Study Design, Accrual, Randomization, Post Randomization Hematologic and Non-Hematologic Adverse Events
Autologous Stem Cell Transplant (ASCT) after
·The study was powered to detect an improvement of 9.6 months
·Drop out rate before randomization is
induction therapy is considered a standard therapy
(prolongation of TTP from 24 months to 33.6 months) in MM patients
projected to be 15% with a study-designed
for ASCT-eligible multiple myeloma (MM) patients.
undergoing a single ASCT.
expected randomization of 462 patients.
Relapse and/or progression of disease are the
·A total of 568 pts were registered at centers from the following cooperative
·Among the 568 registered patients, 459 have
primary causes of treatment failure after ASCT.
groups: CALGB (n=377), ECOG (n=132), and BMT-CTN (n=59).
been randomized, 88 have dropped out and
Thalidomide has been shown to prevent disease
·The study opened in 12/2004 with increasing annual accrual:
21 are pending randomization as of 11/10/09.
progression after ASCT; however up to 40% of
2005, n=33, (6%); 2006, n=62, (11%); 2007, n=137, (24%); 2008, n=214,
·The study closed on 07/03/09.
patients are unable to stay on prolonged
(38%); 2009, n=122, (21%).
·Projected final randomization is ~470.
maintenance. This study was designed to
·Maintenance (Post randomization) CTC Adverse Events from 303 reported
·Randomized patients start at 2 pills daily
determine if lenalidomide would be an effective and
patients receiving study drug and placebo (pooled and not by treatment
(placebo versus 10 mg of lenalidomide) and
tolerable maintenance therapy after single ASCT
arm) are show in Tables I and II
are escalated to 3 pills (placebo versus 15 mg
for MM.
lenalidomide) if tolerated. Patients may be
Table II: Pooled Non-Hematologic Adverse Events
Study Objectives
decreased to 1 pill daily or 1 pill for 3 weeks
·
every month.
Primary Objective
Non Hematologic
CTC Grade 3 CTC Grade 4 CTC Grade 5 Total
·Patients are maintained on lenalidomide until
To determine the efficacy of lenalidomide in
Table 1: Pooled Heme Adverse Events
Adverse Events
N
(%)
N
(%)
N
(%)
progression.
prolonging time to disease progression (TTP) in MM
Cardiac
1
(0)
3
(1)
0
(0)
303
patients after autologous stem cell transplantation
Conclusions
Constitutional
15
(5)
0
(0)
0
(0)
303
Hematologic
CTC Gr 3 CTC Gr 4
CTC Gr 5 Total
(ASCT).
Non CTC AE Death
0
(0)
0
(0)
3
(1)
303
Adverse Events
N
(%) N
(%)
N
(%)
1) This large Phase III study completed
Secondary Objectives
Dermatologic
11
(4)
0
(0)
0
(0)
303
registration and is nearing completion of
Hemoglobin
8
(3)
2
(1)
0
(0)
303
To determine if lenalidomide will increase the CR
GI/Liver/GB/Pancreas
35
(11)
0
(0)
0
(0)
303
patient randomization.
Hemolysis
2
(3)
0
(0)
0
(0)
303
rate in MM patients following ASCT.
Infectious
40
(13)
5
(2)
3
(1)
303
2) Further analysis will determine if there is a
Low Total WBC
15
(5)
2
(1)
0
(0)
303
To compare the progression-free survival (PFS) and
Metabolic/Lab
20
(7)
2
(1)
0
(0)
303
role for maintenance lenalidomide in
overall survival (OS) in MM patients who have
Low Lymph
12
(4)
2
(1)
0
(0)
303
improving TTP.
Neurology/Pain
23
(8)
0
(0)
0
(0)
303
undergone ASCT and who then are randomized to
Low PMNS
51
(17) 24
(8)
0
(0)
303
Pulmonary
9
(3)
5
(2)
0
(0)
303
3) The next MM ASCT Intergroup study
either lenalidomide or placebo.
Low Plts
11
(4)
15
(5)
0
(0)
303
(BMT-CTN 0702) is a 3-arm study: 1) Single
Thrombosis/Embolism
4
(1)
0
(0)
0
(0)
303
To determine the feasibility of long-term
Patients
52
(17) 32
(11) 0
(0)
303
ASCT, 2) Tandem ASCT, 3) Single ASCT
Other
9
(3)
1
(0)
0
(0)
303
administration of lenalidomide to MM patients who
followed by
Max Non-Heme AEs (Pts)
80
(26)
10
(3)
6
(2)
303
have undergone ASCT.
lenalidomide/bortezomib/dexamethasone
Max Overall AE (Patients)
95
(31)
36
(12)
6
(2)
303
·
consolidation. All arms are followed by
·
lenalidomide maintenance for 3 years.
Document Outline