This phase I/II trial studies the side effects and the best dose of lenalidomide when given together with temsirolimus and to see how well it works in treating patients with Hodgkin lymphoma or non-Hodgkin lymphoma that has come back after a period of improvement or is not responding to treatment. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of Hodgkin lymphoma or non-Hodgkin lymphoma by blocking blood flow to the cancer. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide together with temsirolimus may kill more cancer cells.
PRIMARY OBJECTIVES: I. To determine the safety, toxicity, and maximum tolerated dose of lenalidomide when combined with temsirolimus in patients with relapsed lymphomas. (Phase I) II. To determine complete and overall response rate of lenalidomide plus temsirolimus in patients with relapsed lymphomas as stratified by histology: follicular lymphoma, diffuse large B-cell lymphoma, and lymphoma not otherwise specified (NOS) (including Hodgkin lymphoma, T-cell non-Hodgkin lymphoma \[T-NHL\], lymphoplasmacytic lymphoma, and mantle cell lymphoma). (Phase II) III. To determine duration of response, progression-free survival, and overall survival of lenalidomide plus temsirolimus in patients with relapsed lymphomas as stratified by histology: diffuse large B-cell lymphoma, follicular lymphoma, and lymphoma NOS (including Hodgkin lymphoma, T-NHL, lymphoplasmacytic lymphoma, mantle cell lymphoma). (Phase II) SECONDARY OBJECTIVES: I. To determine mammalian target of rapamycin (mTOR) pathway activation in pre-treatment tumor tissue. II. To determine angiogenic and microenvironmental status of pre-treatment tissue and peripheral blood samples, and to evaluate changes following treatment with temsirolimus and lenalidomide. III. To determine differentially expressed genes associated with differences in clinical response and in progression-free survival (PFS) in patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (Groups A and B, respectively). IV. To determine a methylation signature predictive of clinical response and PFS in patients with DLBCL and FL (Groups A and B, respectively). OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study. Patients receive lenalidomide orally (PO) on days 1-21 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses may continue therapy for up to 52 weeks. After completion of study treatment, patients are followed up for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
110
Northwestern University
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Decatur Memorial Hospital
Decatur, Illinois, United States
Ingalls Memorial Hospital
Harvey, Illinois, United States
Illinois CancerCare-Peoria
Peoria, Illinois, United States
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
...and 1 more locations
Incidence of Dose-limiting Toxicity (DLT), Phase I Patients Only
Incidence of dose-limiting toxicity (DLT) defined as any grade 3 or 4 adverse events as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Time frame: 28 days
Complete Response (Phase II)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions;
Time frame: Up to 1 year
Overall Response Rate (Phase II)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 1 year
Progression-free Survival (PFS) (Phase II)
Kaplan-Meier curves will be generated for PFS stratified by histology; median PFS times will be determined and 90% confidence intervals derived as described in Brookmeyer and Crowley.
Time frame: Time from study entry until disease progression or death from any cause, assessed up to 5 years
Overall Survival (OS) (Phase II)
Kaplan-Meier curves will be generated for OS stratified by histology; median OS times will be determined and 90% confidence intervals derived as described in Brookmeyer and Crowley.
Time frame: Time from study entry until death from any cause, assessed up to 6 years
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