HOVON 87 - NMSG 18
RCT comparing
MP-Thalidomide (MP-Thal) followed by thalidomide maintenance
versus
MP-Lenalidomide (MP-Len) followed by lenalidomide maintenance
A joint study of the HOVON and the Nordic Myeloma Study Group
Sponsored by HOVON
Background
With MPT a considerable number of patients develop
relapse or progressive disease in relatively short time
Mean PFS ~2 years
Lenalidomide superior to Thalidomide?
Maintenance therapy?
1
Study design
R
MP-Thalidomide
MP-Lenalidomide
Melfalan 0.18 mg/kg d1-4
9 cycles
9 cycles
Prednisone 2 mg/kg d1-4
Thalidomide 200 mg d1-28/
Lenalidomide 10 mg d1-21
Maintenance
Maintenance
Thalidomide 100 mg d1-28/
Thalidomide
Lenalidomide
Lenalidomide 10 mg d1-21
UNTIL PROGRESSION
Thrombosis prophylaxis aspirin, LMWH in case of previous VTE
In case of ANC < 0.5 or febrile neutropenia PEG-GCSF on day 5 next cycle
Primary objectives
To compare progression free survival
To compare complete and very good partial response
Secondary objectives
Effect of maintenance therapy in terms of improvement of response
Time from relapse/progression to death
Overall survival
Quality of life
2
Statistical considerations
Improvement in PFS in the MPLenalidomide arm with
a relative hazard of 0.67
=0.05 and 80% power
Accrual period of 3 years
452 patients have to be included
Update April 2011
Target number of patients required
452
Patients registered
344
First patient
March 12, 2009
Last patient (expected)
January 2012
Number of participating centers:
Netherlands
45
Belgium
2
Norway
12
Denmark
3
Sweden
11
3
Patient characteristics
A: MP+Thal
B: MP+Len
Total
Total
166
166
332
Age (median, range)
72 (60-87)
72 (64-87)
72 (60-87)
Gender (M/F, %M)
94/72
93/73
187/145
(56.6%)
(56.0%)
(56.3%)
ISS stage
I
27%
26%
26%
II
46%
43%
45%
IIII
27%
31%
29%
Efficacy data
4
Incidence of SAE's
Nr of patients with at least one SAE
155 (47%)
Number of SAE per person
# 1 SAE
91 (27%)
# 2 SAE
43 (13%)
# 3-7 SAE
21 (7%)
General causes of SAE's
Reason SAE
Death
8 (5%)
Life threatening
7 (5%)
Hospitalisation
128 (83%)
Disability
5 (3%)
Other
7 (5%)
1st cycle
107
Total
155
DSMB no reason for amendments
No difference <75 versus 75 years
5
Side studies
Molecular characterization
Biological diversity - Prognostic value - Predictive value
Imaging studies
Monitoring therapy response
Molecular characterization
Gene Expression Profiling
Single Nucleotide Polymorphism analysis
Investigating variation in gene expression and in genes
representing cellular functions and pathways that determine
Biology of the disease
Course of the disease
Treatment efficacy
Treatment related toxicity
6
Imaging studies
Prognostic value of different imaging techniques at diagnosis
Conversion rate of PET in non-intensively treated patients
WB-MRI
N=60
FDG-PET-CT
1 cycle MPT/L
WB-XR
*
2 cycles MPT/L
WB-MRI
FDG-PET-CT
2 cycles MPT/L
N=30
2 cycles MPT/L
2 cycles MPT/L
WB-MRI
FDG-PET-CT
maintenance
Results of MRI and PET-CT are
thalidomide/lenalidomide
blinded
Acknowledgments
PARTICIPATING CENTERS
Co-investigators HOVON
Gerard Bos, Netherlands
Pieter Sonneveld, Netherlands
Co-investigators NMSG
Anders Waage, Norway
Ulf Henrik Mellqvist, Sweden
Morton Salomo, Denmark
NMSG and HOVON DATA CENTER
Cees van Montfort, statistics
Heleen Visser/Rianne Ammerlaan, trial coördinators
Celgene for financial support
7