Lenalidomide After Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancers
Lenalidomide After Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancers
This phase I clinical trial is studying the side effects and the best dose of lenalidomide
 after donor bone marrow transplant in treating patients with high-risk hematologic cancer.
 Biological therapies, such as lenalidomide, may stimulate the immune system in different ways
 and stop cancer cells from growing.
PRIMARY OBJECTIVES:

 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
 patients.

 SECONDARY OBJECTIVES:

 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
 anti-tumor effect.

 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.
Inclusion Criteria:

 -  Histologically confirmed hematologic malignancy meeting 1 of the following criteria:

 -  High-risk acute myeloid leukemia meeting 1 the following criteria:

 -  First complete response (CR) and ≥ 60 years of age OR < 60 years of age with
 high-risk cytogenetics as defined by CALGB OR high-molecular risk and not
 eligible or willing to undergo myeloablative conditioning

 -  Second or later complete remission

 -  Not in remission but with < 5% blasts within 3 weeks of start of
 conditioning chemotherapy for allogeneic transplantation

 -  Patients with a history of CNS involvement allowed provided disease is in
 remission at the time of transplantation

 -  Patients with non-Hodgkin lymphoma who are candidates for allogeneic stem cell
 transplantation will be eligible; patients who have relapsed status post
 autologous transplantation are eligible as long as they demonstrate chemotherapy
 sensitive disease; patients with a history of CNS involvement are eligible if
 this aspect of the disease is in remission at the time of transplantation

 -  High-risk chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL),
 or primary and secondary B-prolymphocytic leukemia (PLL) meeting 1 of the
 following criteria:

 -  del(17p13.1) disease that has been treated (may have been given as
 consolidation therapy)

 -  Less than PR to chemoimmunotherapy or relapsed within 2 years of treatment

 -  Nucleoside analog refractory disease or disease that relapsed after two
 prior regimens

 -  Patients with Richter (large cell) transformation allowed provided the large
 cell component of the disease is in remission (< 10% large cells in the bone
 marrow allowed)

 -  Patient has undergone an allogeneic stem cell transplantation using a
 reduced-intensity or non-myeloablative conditioning regimen within the past 60 days

 -  At least 40% T-cell donor chimerism at day 30

 -  ECOG performance status 0-2 (Karnofsky 60-100%)

 -  Life expectancy > 3 months

 -  Myeloid engraftment with absolute neutrophil count > 1,000/μL and platelet count >
 50,000/μL (after allogeneic hematopoietic stem cell transplantation [AHSCT])

 -  Total bilirubin normal

 -  AST and ALT ≤ 2.5 times upper limit of normal (ULN)

 -  AST < 3 times ULN after AHSCT

 -  Creatinine clearance ≥ 50 mL/min in stratum 1 or ≥ 30 mL/min in stratum 2

 -  DLCO > 40% with no symptomatic pulmonary disease

 -  LVEF ≥ 30% by echocardiogram or MUGA

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must agree to use two acceptable methods of contraception (one highly
 effective method and one additional effective method) or practice abstinence for ≥ 28
 days before, during, and ≥ 28 days after completing lenalidomide

 -  HIV negative

 -  No uncontrolled infection requiring intravenous therapy or poorly controlled diabetes
 mellitus

 -  No history of allergic reactions attributed to compounds of similar chemical or
 biologic composition to lenalidomide

 -  No uncontrolled intercurrent illness including, but not limited to, any of the
 following:

 -  Ongoing or active infection

 -  Symptomatic congestive heart failure

 -  Unstable angina pectoris

 -  Cardiac arrhythmia

 -  Psychiatric illness and/or social situations that would limit compliance with
 study requirements

 -  No history of grade 3 or 4 graft-vs-host disease (GVHD)

 -  If patient has acute GVHD grade 1 or 2, GVHD must be controlled and dose of oral
 prednisone or equivalent ≤ 20 mg per day (after AHSCT)

 -  More than 4 weeks since prior chemotherapy (excluding steroids), radiotherapy, or
 radioimmunoconjugate therapy (6 weeks for nitrosoureas or mitomycin C) and recovered

 -  No other concurrent investigational agents