Lenalidomide Maintenance Therapy in Multiple Myeloma: A Phase II Clinical and Biomarker Study
Multiple myeloma (MM) remains largely an incurable disease with an estimated median survival
of 6-7 years in standard risk myeloma and 2-3 years in high risk disease despite treatment
with autologous stem cell transplantation (ASCT).
Maintenance therapy to achieve sustained suppression of residual disease following
chemotherapy or ASCT has long been viewed as a desirable approach for extending survival in
Giving the immunomodulatory drug lenalidomide after induction or re-induction treatment may
stimulate the immune system in various ways to stop or slow the return of cancer.
It is not yet known how immune stimulatory effects of extended dosing with lenalidomide in
the maintenance setting correlate with clinical benefits.
Assess T cell (CD4, CD8), NKT and NK cell numbers in peripheral blood during the
course of lenalidomide maintenance therapy in treated MM patients.
Determine progression free survival
Determine duration of response
Assess NK cell function and activity
Assess changes in B cell subsets, myeloid derived suppressor cells (MDSC) and T regulatory
cells by phenotypic analysis during the course of therapy
Assess expression of cereblon (CRBN), and how it relates to NK cell number and activity
Patients with multiple myeloma who have achieved stable disease or better response, assessed
at greater than or equal to 4 weeks after completing induction or re-induction treatment
Age greater than or equal to 18 years
ECOG PS of 0-2
Adequate hematological parameters defined by: absolute neutrophil count greater than or
equal to 1.0 K/microL, hemoglobin greater than or equal to 8 g/dL, and platelet count
greater than or equal to 75 K/microL
Adequate hepatic function, with bilirubin < 1.5 times the ULN, and AST and ALT < 2.5 times
Adequate renal function with creatinine clearance (CrCl) of greater than or equal to 40
mL/min. CrCl will be calculated using the Cockcroft-Gault method. If the calculated CrCl
based on Cockcroft-Gault method is < 40 mL/min, patient will have a 24 hr urine collection
to measure CrCl. The measured CrCl must also be greater than or equal to 40 ml/min
Single arm, single stage, phase II trial of lenalidomide maintenance for treated MM patients
who have stable or responsive disease.
After screening, eligibility determination, and enrollment; subjects will receive
lenalidomide 10 mg by mouth daily on days 1-21 of repeated 28-day cycles. When necessary,
lenalidomide will be held and restarted in accordance with accepted clinical dose
Subjects may continue lenalidomide until disease progression or unacceptable toxicity.
Blood will be obtained to assess changes in T cell (CD4, CD8), NKT and NK cell numbers by
flow-cytometric analysis at pre-specified time points during lenalidomide maintenance.
Blood samples and/or bone marrow samples where possible, will be used for additional
research studies, which may include functional analyses of immune-cell subsets, analyses for
cytokines, chemokines, antibodies, tumor cell antigen targets, and/or other markers.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Longitudinal assessment of T cell, NKT and NK cell counts
Carl O Landgren, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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