Lenalidomide and Temsirolimus in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01076543
First received: February 25, 2010
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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 relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma. 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.


Condition Intervention Phase
Adult Grade III Lymphomatoid Granulomatosis
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
HIV-associated Hodgkin Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Post-transplant Lymphoproliferative Disorder
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: lenalidomide
Drug: temsirolimus
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Investigation of Temsirolimus Plus Lenalidomide in Relapsed Non-Hodgkin Lymphomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Maximum-tolerated dose (MTD) based on the incidence of DLT as graded by the NCI CTCAE version 4.0 (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Complete response (Phase II) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Overall response rate (Phase II) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (PFS) (Phase II) [ Time Frame: Time from study entry until disease progression or death from any cause, assessed up to 1 year ] [ Designated as safety issue: No ]
    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.

  • Overall survival (OS) (Phase II) [ Time Frame: Time from study entry until death from any cause, assessed up to 1 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 150
Study Start Date: April 2010
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (lenalidomide, temsirolimus)
Patients receive lenalidomide PO on days 1-21 and temsirolimus 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.
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histology: bone marrow biopsies (with the exception of lymphoplasmacytic lymphoma) as the sole means of diagnosis are not acceptable; fine needle aspirates are not acceptable

    • Phase I: previously treated, histologically confirmed Hodgkin and non-Hodgkin lymphomas; the only exception to a requirement for a lymph node biopsy is lymphoplasmacytic lymphoma, which can be diagnosed based on morphologic evidence in the bone marrow plus the appropriate paraprotein
    • Phase II: previously treated, histologically confirmed mature non-Hodgkin lymphoma (NHL) stratified by histology:

      • Group A: diffuse large B-cell lymphoma (NOTE: all patients with DLBCL must have germinal center vs. non-germinal center phenotype established via immunohistochemistry)
      • Group B: follicular lymphoma
      • Group C: lymphoma NOS (including Hodgkin lymphoma, T-NHL, marginal zone lymphoma, lymphoplasmacytic
  • No limit to number of prior therapies; prior autologous transplantation is allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count (ANC) >= 1,000/uL
  • Platelet count >= 75,000/uL
  • Total bilirubin =< 1.5 times upper limit of normal (ULN) (unless due to Gilbert's)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times ULN
  • Creatinine clearance >= 60 mL/min as determined by calculated Cockcroft-Gault equation
  • Fasting serum cholesterol =< 350 mg/dL
  • Fasting serum triglycerides =< 2.5 times ULN
  • All patients are required to have measurable disease; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable include the following:

    • Bone lesions (lesions if present should be noted)
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Bone marrow (involvement by lymphoma should be noted)
    • For Waldenstrom's macroglobulinemia, measurable disease is defined as at least one lesion with a single diameter of greater than 2 cm by computed tomography or bone marrow involvement with greater than 10% malignant cells and quantitative monoclonal protein (immunoglobulin M [IgM], IgG, IgA) greater than 1,000 mg/dL
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients who are human immunodeficiency virus (HIV) positive are allowed to participate BUT must meet the following criteria:

    • No acquired immune deficiency syndrome (AIDS)-defining illness, AND
    • Cluster of differentiation (CD) 4 count >= 400 cells/mm^3, AND
    • No anti-retroviral therapy (including high-active antiretroviral therapy [HAART]) within 7 days of starting protocol therapy, AND
    • Patient may not take concurrent anti-retroviral therapy (including HAART) while on protocol
    • NOTE: it is not generally recommended to suspend anti-retroviral therapy (including HAART); the medical team enrolling a patient who suspends anti-retroviral therapy for the purpose of study participation must have a documented note reviewing the potential risks/benefits with the patient in the medical chart

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biological composition to temsirolimus or lenalidomide used in study
  • Patients requiring active anti-retroviral therapy for HIV are excluded
  • No "currently active" second malignancy, other than non-melanoma skin cancers; patients are not considered to have a "currently active" second malignancy if they have completed anti-cancer therapy and are considered by their physicians to be at less than 30% risk of relapse
  • No history (within 3 months of study entry) of deep venous thrombosis/pulmonary embolism (DVT/PE); patients with a distant history (greater than 3 months before study entry) of DVT/PE are eligible, but should receive prophylactic aspirin or low molecular weight heparin
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with relapsed/refractory DLBCL or HL who are eligible and willing to undergo potentially curative stem cell transplant
  • Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are excluded
  • No corticosteroids within 14 days prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 10 mg/day prednisone or equivalent; any patient on steroid therapy must receive thromboembolic prophylaxis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01076543

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Adam M. Petrich    312-695-4537    apetrich@nmff.org   
Principal Investigator: Adam M. Petrich         
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Sonali M. Smith    773-834-2895    smsmith@medicine.bsd.uchicago.edu   
Principal Investigator: Sonali M. Smith         
Decatur Memorial Hospital Recruiting
Decatur, Illinois, United States, 62526
Contact: James L. Wade    217-876-6600    Jlwade3@aol.com   
Principal Investigator: James L. Wade         
Ingalls Memorial Hospital Recruiting
Harvey, Illinois, United States, 60426
Contact: Mark F. Kozloff    708-339-4800    mfkozloff@aol.com   
Principal Investigator: Mark F. Kozloff         
Illinois CancerCare-Peoria Recruiting
Peoria, Illinois, United States, 61615
Contact: Paul A. Fishkin    309-243-3000    pfishkin@illinoiscancercare.com   
Principal Investigator: Paul A. Fishkin         
Central Illinois Hematology Oncology Center Recruiting
Springfield, Illinois, United States, 60702
Contact: Edem S. Agamah    217-525-2500    ihdn@aol.com   
Principal Investigator: Edem S. Agamah         
Southern Illinois University Recruiting
Springfield, Illinois, United States, 62702
Contact: Krishna A. Rao    217-545-7969    krao@siumed.edu   
Principal Investigator: Krishna A. Rao         
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc-Parkview Recruiting
Fort Wayne, Indiana, United States, 46845
Contact: Sreenivasa R. Nattam    260-484-8830    ledgar@fwmoh.com   
Principal Investigator: Sreenivasa R. Nattam         
Indiana University Medical Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Noah M. Hahn    317-278-6871    nhahn@iupui.edu   
Principal Investigator: Noah M. Hahn         
United States, Maryland
University of Maryland/Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Amy S. Kimball    410-328-2703    akimball@umm.edu   
Principal Investigator: Amy S. Kimball         
United States, Missouri
Saint John's Mercy Medical Center Recruiting
Saint Louis, Missouri, United States, 63141
Contact: Bethany G. Sleckman    314-251-7057    slecbg@stlo.mercy.net   
Principal Investigator: Bethany G. Sleckman         
Sponsors and Collaborators
Investigators
Principal Investigator: Sonali Smith University of Chicago Phase 2 Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01076543     History of Changes
Other Study ID Numbers: NCI-2011-01456, NCI-2011-01456, CDR0000666432, 09-443-A, 8309, P30CA014599, N01CM00071, N01CM62201
Study First Received: February 25, 2010
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Lymphomatoid Granulomatosis
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Intraocular Lymphoma
Lymphoma, Mantle-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections

ClinicalTrials.gov processed this record on August 18, 2014