A Phase 1 Study of Lenalidomide Maintenance Following Allogeneic Hematopoietic Cell Transplantation in Patients With Select High Risk Hematological Malignancies
I. Determine the maximal-tolerable dose (MTD) of lenalidomide after allogeneic hematopoietic
stem cell transplantation (AHSCT) in patients with advanced acute myeloid leukemia (AML),
non-Hodgkin's lymphoma (NHL), or chronic lymphocytic leukemia (CLL).
II. Define the qualitative and quantitative toxicities of lenalidomide in regard to organ
specificity, time course, predictability, and reversibility following AHSCT in these
I. Determine the anti-tumor response in patients treated with lenalidomide after AHSCT when
compared with historical controls.
II. Evaluate the plasma and cellular pharmacokinetics of lenalidomide in patients enrolled
on this study and interactions with supportive agents such as calcineurin inhibitors.
III. Evaluate the frequency of acute and chronic graft-vs-host disease and graft failure in
patients enrolled on this study.
IV. Prospectively assess the feasibility of administering an oral agent post-transplant as
measured by efficiency of patients being registered to therapy early and also meeting
eligibility criteria for lenalidomide treatment.
V. Perform pharmacodynamic studies following lenalidomide treatment including development of
B, T, and myeloid cell chimerism; assessment of immune activation; cytokines; tumor cell
expression of co-stimulatory molecules; development of anti-tumor antibodies and
immunoglobulin recovery; and re-expression of microRNAs that may mediate lenalidomide
OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to
diagnosis (high-risk acute myeloid leukemia vs non-Hodgkin lymphoma vs high-risk chronic
lymphocytic leukemia, small lymphocytic lymphoma, or B-prolymphocytic leukemia).
Patients receive oral lenalidomide once daily on days 1-28. Courses repeat every 28 days for
up to 24 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and bone marrow biopsies and aspirate collection at baseline and
periodically during study for pharmacokinetic and pharmacodynamic studies. Buccal swab
samples are also collected at baseline and analyzed for genetic polymorphisms.
After completion of study therapy, patients are followed up for up to 1 year.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of lenalidomide after allogeneic hematopoietic stem cell transplantation graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Up to day 28
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|