Know Cancer

forgot password

Phase I/II Investigation of Temsirolimus Plus Lenalidomide in Relapsed Non-Hodgkin Lymphomas

Phase 1/Phase 2
18 Years
Open (Enrolling)
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, 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 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, Recurrent Small Lymphocytic Lymphoma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenström Macroglobulinemia

Thank you

Trial Information

Phase I/II Investigation of Temsirolimus Plus Lenalidomide in Relapsed Non-Hodgkin Lymphomas


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 NOS (including Hodgkin lymphoma, T-NHL, lymphoplasmacytic lymphoma,
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)


I. To determine 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 DLBCL and 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 multicenter, phase I, dose-escalation study of lenalidomide followed by a
phase II study.

Patients in the phase II portion are stratified according to non-Hodgkin lymphoma (NHL)
histology (diffuse large-B-cell lymphoma vs follicular lymphoma vs lymphoma not otherwise
specified [Hodgkin lymphoma, T-NHL, marginal zone lymphoma, and lymphoplasmacytic

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.

Some patients undergo blood samples collection at baseline and periodically during study for
laboratory analysis by ELISA and flow cytometry. Tumor tissues from biopsies are also

Inclusion Criteria:

- Histologically confirmed relapsed or refractory lymphoma

- Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) (phase I)

- Mature NHL, including the following cell types (phase II):

- Diffuse large B-cell lymphoma (DLBCL) with germinal center versus
non-germinal center phenotype as established by IHC

- Follicular lymphoma

- Lymphoma not otherwise specified (e.g., HL, T-NHL, marginal zone lymphoma,
lymphoplasmacytic lymphoma)

- No chronic lymphocytic leukemia or small lymphocytic lymphoma

- No bone marrow biopsies (with the exception of lymphoplasmacytic lymphoma) as sole
means of diagnosis

- Fine needle biopsies not allowed

- Must have received prior therapy

- Measurable disease, defined as any tumor mass > 1 cm

- Non-measurable disease alone, including the following, is not allowed:

- Bone lesions

- Ascites

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonis

- Bone marrow

- Waldenstrom's macroglobulinemia

- For Waldenstrom's macroglobulinemia measurable disease is defined as ≥
1 lesion with a single diameter of > 2 cm by CT or bone marrow
involvement > 10% malignant cells and quantitative monoclonal protein
(IgM, IgG, IgA) > 1,000 mg/dL

- No known CNS involvement

- No patients with relapsed or refractory DLBCL or HL who are eligible and willing to
undergo potentially curative stem cell transplantation

- ECOG performance status 0-2

- ANC ≥ 1,000/μL

- Platelet count ≥ 75,000/μL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Gilbert

- AST/ALT ≤ 2.5 times ULN

- Creatinine clearance ≥ 60 mL/min

- Fasting serum cholesterol ≤ 350 mg/dL

- Fasting serum triglycerides ≤ 2.5 times ULN

- Not pregnant or nursing

- Two negative pregnancy tests (i.e., first test within 10-14 days before lenalidomide
and second test within 24 hours of starting lenalidomide)

- Fertile patients must agree to continue abstinence or begin using 2 methods of
effective contraception (one highly effective and one additional effective method) at
the same time for ≥ 28 days prior to start lenalidomide

- HIV-positive patients allowed provided the following criteria are met:

- No AIDS-defining illness

- CD4 count ≥ 400 cells/mm^3

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

- No currently active second malignancy other than nonmelanoma skin cancers

- Patients who have completed anticancer therapy for second malignancy and are
considered by their physicians to have < 30% risk of relapse allowed

- No deep venous thrombosis/pulmonary embolism (DVT/PE) within the past 3 months

- Patients with DVT/PE > 3 months ago must receive prophylactic aspirin or
low-molecular weight heparin

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

- 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 other concurrent anticancer commercial agents or therapies

- Any number of prior therapies allowed, including prior autologous transplantation

- More than 4 weeks since prior and no other concurrent chemotherapy or radiotherapy (6
weeks for nitrosoureas or mitomycin C) and recovered

- More than 7 days since prior and no concurrent antiretroviral therapy (including

- No corticosteroids within the past 14 days except for maintenance of non-malignant

- Prednisone or equivalent maintenance therapy dose < 10 mg/day

- No concurrent dexamethasone or other steroidal antiemetics

- No concurrent pegfilgrastim

- No other concurrent investigational agents

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability of the combination of lenalidomide and temsirolimus (Phase I)

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Sonali Smith

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Phase 2 Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

April 2010

Completion Date:

Related Keywords:

  • 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
  • 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 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
  • Recurrent Small Lymphocytic Lymphoma
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
  • Burkitt Lymphoma
  • Hodgkin Disease
  • Immunoblastic Lymphadenopathy
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • 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
  • Lymphoma, Mantle-Cell



Medical University of South Carolina Charleston, South Carolina  29425-0721
Loyola University Medical Center Maywood, Illinois  60153
Ingalls Memorial Hospital Harvey, Illinois  60426
Central Illinois Hematology Oncology Center Springfield, Illinois  62701
Northwestern University Chicago, Illinois  60611
Indiana University Medical Center Indianapolis, Indiana  46202
Decatur Memorial Hospital Decatur, Illinois  62526
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Northern Indiana Cancer Research Consortium South Bend, Indiana  
Froedtert and the Medical College of Wisconsin Milwaukee, Wisconsin  53226
Evanston CCOP-NorthShore University HealthSystem Evanston, Illinois  60201
Illinois CancerCare-Peoria Peoria, Illinois  61615
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard Fort Wayne, Indiana  46845
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
University of Maryland Greenebaum Cancer Center Baltimore, Maryland  21201
Oncology Care Associates PLLC St. Joseph, Michigan  49085
University of Michigan University Hospital Ann Arbor, Michigan  48109
Southern Illinois University Springfield, Illinois  62702