Lenalidomide, Rituximab, and Combination Chemotherapy in Treating Patients with Newly Diagnosed Stage II-IV Diffuse Large Cell or Grade 3A / B Follicular B-Cell Lymphoma

Status: Active


This phase I / II trial studies the side effects and best dose of lenalidomide when given together with rituximab and combination chemotherapy and to see how well it works in treating patients with newly diagnosed stage II-IV diffuse large cell lymphoma or grade 3 follicular grade B-cell lymphoma. Lenalidomide may help the immune system kill abnormal blood cells or cancer cells and may also prevent the growth of new blood vessels that tumors need to grow. Monoclonal antibodies, such as rituximab, bind to a protein on the surface of cancer cells and activate the immune system to kill the cells. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lenalidomide together with rituximab and combination chemotherapy may kill more cancer cells.

Eligibility Criteria

Inclusion Criteria

  • One of the following untreated, histological confirmed lymphoma expressing cluster of differentiation (CD)20 antigen * DLBCL with disconcordant and/or composite pathology e.g. low grade follicular lymphoma within bone marrow or lymph node are eligible * DLBCL transformation follicular lymphoma (FL) – untreated with anthracyclines or high dose chemotherapy/autologous stem cell transplantation; patients treated with rituximab alone, non-anthracycline containing regiments and previously observed only are eligible
  • Stages II, III, or IV (Ann Arbor Staging)
  • Measurable disease (at least 1 lesion of >= 1.5 cm in one diameter) as detected by computed tomography (CT) or the CT images of the positron emission tomography (PET)/CT (PET/CT fusion); skins lesions can be used if the area is greater than or equal to 2 cm in at least one diameter and photographed with a ruler
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1500 obtained =< 14 days prior to registration
  • Platelets (PLT) >= 100,000 obtained =< 14 days prior to registration
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN, the direct bilirubin must be normal obtained =< 14 days prior to registration
  • Alkaline (Alk.) phosphatase =< 3 x ULN unless evidence of the direct liver involvement by lymphoma - then =< 5 x ULN obtained =< 14 days prior to registration
  • Aspartate aminotransferase (AST) =< 3 x ULN unless evidence of the direct liver involvement by lymphoma - then =< 5 x ULN obtained =< 14 days prior to registration
  • Creatinine =< 2 x ULN obtained =< 14 days prior to registration
  • Females of reproductive potential must be willing to adhere to the scheduled pregnancy testing as required in the REVLIMID Risk Evaluation and Mitigation Strategy (REMS) program
  • Willingness to provide informed written consent
  • Willingness to return to enrolling institution for follow-up
  • Patient willing to provide blood samples for research purposes
  • Patients who are not already on anticoagulation should be able to take low-dose aspirin (81 mg) daily; NOTE: if aspirin is contraindicated for other reasons, the patient may be considered for the study after consultation with the study chair regarding other alternatives including possible use of warfarin or low molecular weight heparin; patients unable to take any form of prophylaxis are not eligible
  • Willing to be registered into the mandatory REVLIMID REMS program, and willing and able to comply with the requirements of the REVLIMID REMS program

Exclusion Criteria

  • Pregnant women
  • Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide)
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Known to be human immunodeficiency virus (HIV) positive or immunocompromised with posttransplant lymphoproliferative disorder (PTLD)
  • 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
  • Receiving any other agent which would be considered as a treatment for the lymphoma
  • Another active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy; exceptions to this are as follows: localized non-melanotic skin cancer and any cancer that in the judgment of the investigator has been treated with curative intent and will not interfere with the study treatment plan and response assessment; patients with >= 25% of the bone marrow radiated for other diseases are not eligible
  • History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Ejection fraction of < 45% by either multi gated acquisition scan (MUGA) or echocardiogram (ECHO)
  • History of life threatening or recurrent thrombosis/embolism; patients may participate if they are on anticoagulation during the treatment
  • Receiving erythroid stimulating agents (erythropoietin [EPO]: Procrit, Aranesp)

Locations & Contacts


Mayo Clinic
Status: Active
Contact: Grzegorz S. Nowakowski
Phone: 507-284-2511
Email: nowakowski.grzegorz@mayo.edu

Trial Objectives and Outline


I. To assess the safety and efficacy of lenalidomide in combination with standard induction therapy (rituximab, cyclophosphamide, doxorubicin [doxorubicin hydrochloride], vincristine [vincristine sulfate] and prednisone - [RCHOP]) in patients with newly diagnosed diffuse large cell and follicular grade IIIA/B B-cell lymphoma.

II. To establish the maximum tolerated dose of lenalidomide in combination with RCHOP chemotherapy. (Phase I)

III. To assess the efficacy (event-free survival and response rate) and safety of this combination. (Phase II)


I. To assess the host immune function at baseline and after treatment and how these parameters relate to tumor response and event-free survival.

II. To assess the efficacy of this combination in diffuse large B-cell lymphoma (DLBCL) patients with activated B-cell-like lymphoma.

III. To assess the safety and efficacy of lenalidomide, rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R2CHOP) in patients with transformed or composite follicular lymphoma.

OUTLINE: This is a phase I dose-escalation study of lenalidomide followed by a phase II study.

Patients receive rituximab intravenously (IV), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1; prednisone orally (PO) on days 1-5; and lenalidomide PO on days 1-10. Patients also receive pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for year 1, every 4 months for year 2, and then every 6 months for 3 years.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type


Lead Organization

Lead Organization
Mayo Clinic

Principal Investigator
Grzegorz S. Nowakowski

Trial IDs

Primary ID MC078E
Secondary IDs NCI-2009-01196, RV-NHL-PI-0325, Celgene #RV-NHL-PI-0325
Clinicaltrials.gov ID NCT00670358