Randomized Phase III Trial of Bortezomib, Lenalidomide and Dexamethasone (VRd) Versus Carfilzomib, Lenalidomide, Dexamethasone (CRd) Followed by Limited or Indefinite Lenalidomide Maintenance in Patients With Newly Diagnosed Symptomatic Multiple Myeloma
PRIMARY OBJECTIVES:
I. To compare the overall survival between two strategies of lenalidomide maintenance
following induction with a proteasome inhibitor-IMiD (lenalidomide) combination: limited
duration of maintenance (24 months) versus indefinite maintenance therapy until disease
progression.
SECONDARY OBJECTIVES:
I. To compare the progression-free survival between two strategies of lenalidomide
maintenance following induction with a proteasome inhibitor-IMiD combination: limited
duration of maintenance (24 months) or indefinite maintenance therapy until disease
progression.
II. To compare progression-free survival between bortezomib, lenalidomide, and dexamethasone
(VRd) and carfilzomib, lenalidomide, and dexamethasone (CRd) induction followed by
lenalidomide maintenance in patients with newly diagnosed symptomatic multiple myeloma.
III. To compare induction rates of response between VRd and CRd arms. IV. To evaluate time
to progression, duration of response and overall survival between VRd and CRd induction
therapy.
V. To compare induction rates of toxicity between VRd and CRd arms. VI. To evaluate toxicity
during lenalidomide maintenance.
TERTIARY OBJECTIVES:
I. To compare the short and long-term health-related quality of life impact between two
strategies of lenalidomide maintenance following induction with a proteasome inhibitor-IMiD
combination: limited duration of maintenance (24 months) versus indefinite maintenance
therapy until disease progression.
II. To compare the impact on health-related quality of life between VRd and CRd induction
therapy.
III. To evaluate the association between early induction response and change in
health-related quality of life.
IV. To describe changes in health-related quality of life during the induction, active
maintenance and observation phases.
V. To evaluate correlation between treatment adherence during maintenance and health-related
quality of life.
VI. To compare induction minimal residual disease negativity rates between VRd and CRd arms.
VII. To compare minimal residual disease negativity rates between two strategies of
lenalidomide maintenance following induction with a proteasome inhibitor-IMiD combination:
limited duration of maintenance (24 months) versus indefinite maintenance therapy until
disease progression.
VIII. To describe changes in minimal residual disease during the induction, active
maintenance and observation phases and explore association with response.
IX. To evaluate gene expression profiles of tumor cells at baseline among standard risk
patients and explore the development of a prognostic gene expression signature for standard
risk myeloma.
X. To evaluate changes in gene expression profiles of tumor cells following treatment and
elucidate response and resistance mechanisms.
OUTLINE:
INDUCTION: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4,
8, and 11 of courses 1-8 and days 1 and 8 of courses 9-12; lenalidomide orally (PO) daily on
days 1-14; and dexamethasone PO daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of courses 1-8
and days 1, 2, 8, and 9 of courses 9-12. Treatment repeats every 3 weeks for 12 courses in
the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16;
lenalidomide PO daily on days 1-21; and dexamethasone PO on days 1, 8, 15, and 22. Treatment
repeats every 4 weeks for 9 courses in the absence of disease progression or unacceptable
toxicity.
MAINTENANCE: After completion of induction therapy, patients are then randomized to 1 of 2
maintenance treatment arms.
ARM C: Patients receive lenalidomide PO daily on days 1-21. Treatment repeats every 4 weeks
for 24 courses in the absences of disease progression or unacceptable toxicity.
ARM D: Patients receive lenalidomide PO daily on days 1-21. Courses repeat every 4 weeks in
the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then annually for 10 years.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival for the maintenance analysis
The Kaplan-Meier (KM) method will be used to describe the overall survival function by arm.
From the maintenance randomization to death due to any cause or, censored at the date last known alive, assessed up to 15 years
No
Shaji Kumar
Principal Investigator
Eastern Cooperative Oncology Group
United States: Federal Government
E1A11
NCT01863550
November 2013
Name | Location |
---|---|
Eastern Cooperative Oncology Group | Boston, Massachusetts 02215 |