Rituximab and Combination Chemotherapy with or without Lenalidomide in Treating Patients with Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and overE1412
NCI-2013-00959, ECOG-E1412, NCT01856192

Trial Description

Summary

This randomized phase II trial studies how well rituximab and combination chemotherapy with or without lenalidomide work in treating patients with newly diagnosed stage II-IV diffuse large B cell lymphoma. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. 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. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether rituximab and combination chemotherapy are more effective when given with or without lenalidomide in treating patients with diffuse large B cell lymphoma.

Further Study Information

PRIMARY OBJECTIVES:

I. Progression-free survival (PFS).

SECONDARY OBJECTIVES:

I. Response rate (RR).

II. Complete remission (CR) rate as defined by positron emission tomography (PET)-computed tomography (CT) criteria.

III. Overall survival (OS).

TERTIARY OBJECTIVES:

I. Impact of diffuse large B cell lymphoma (DLBCL) molecular subtype on outcome.

II. Interim PET scan results in relation to treatment outcome.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: 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. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone as in Arm A. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patient are followed up every 3 months for 2 years, every 6 months for 1 year, and then annually for up to 7 years.

Eligibility Criteria

Inclusion Criteria:

PRE-REGISTRATION (STEP 0)

Histologically confirmed DLBCL expressing cluster of differentiation (CD)20 antigen; patients with transformed lymphoma are excluded; in this regard, patients with composite lymphoma in the diagnostic tissue (concomitant DLBCL and follicular or other low-grade lymphoma component) are excluded; however, patients with DLBCL in primary diagnostic tissue but a bone marrow that shows low grade or indeterminate lymphoma are eligible; patients with known primary mediastinal large B-cell lymphoma (PMLBCL) are excluded; similarly, patients with known v-myc myelocytomatosis viral oncogene homolog (avian) (c-myc) translocation (by fluorescence in situ hybridization) positive DLBCL are encouraged to participate in trials specifically designed for these patients; however patients with known c-myc DLBC positive are NOT excluded from this study; c-myc testing prior to study enrollment is NOT required

Stages II bulky disease (defined as mass size of more than 10 cm), stage III, or IV (Ann Arbor staging); patients with stage I and stage II non-bulky disease are excluded from this study

A paraffin-embedded tumor tissue specimen from the initial diagnostic biopsy has been located and ready to ship to the Mayo Clinic Lymphoma Laboratory following pre-registration; Note: exisional tumor biopsy is preferred; core needle biopsies will be considered adequate if there is enough tissue for the mandatory central pathology review immunohistochemistry and Genomics Education Partnership (GEP); submission of a tumor block is preferred, but if unavailable submit alternative materials

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Previously untreated and not receiving any other agent that would be considered as a treatment for the lymphoma; for subjects with severe systemic symptoms, compressive disease, or rapidly progressing symptomatic adenopathy, are allowed for lymphoma associated symptom treatment with up to 1 mg/kg/day prednisone, or equivalent, for a maximum of 7 days is permitted prior to beginning the treatment, at the discretion of the investigator; a washout period does not apply

No known central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells; these patients are usually treated with CNS directed therapy; screening for cerebrospinal fluid (CSF)/CNS involvement is NOT required but can be performed per treating medical doctor (MD) discretion; intrathecal (IT) methotrexate or IT cytarabine prophylaxis in patients with negative CSF who are felt to be at high risk of CNS relapse is allowed per local MD discretion; this should be noted on the treatment form

Absence of history of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

Absence of history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia; patients with a history of deep vein thrombosis(DVT)/pulmonary embolism (PE) or thrombophilia may participate if they are willing to be on full anticoagulation during the treatment if randomized to rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R2CHOP) arm A; full anticoagulation is defined as warfarin, factor X inhibitors, or low molecular weight heparin at therapeutic doses

Patient must be able and willing to receive anticoagulation therapy with aspirin 70-325 mg daily prophylaxis, low molecular weight heparin, factor X inhibitors or warfarin; patients unable or unwilling to take any prophylaxis are NOT eligible

Absence of history of acquired immune deficiency syndrome (AIDS)-related conditions (other than the presenting DLBCL) or post-transplant lymphoproliferative disorder (PTLD) in immunocompromised patients; patients with human immunodeficiency virus (HIV) on antiretroviral therapy other than zidovudine (AZT) and/or stavudine and without prior AIDS defining conditions and adequate CD4 count (> 400) are eligible

No other 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

No history of radiation therapy to >= 25% of the bone marrow for other diseases or history of anthracycline therapy

Patients must not be receiving erythroid stimulating agents (erythropoietin [EPO]: Procrit, Aranesp)

RANDOMIZATION (STEP 1)

Patient meets the eligibility criteria outlined above

Site has received notification from Mayo Clinic – Rochester Division of Hematopathology of the central confirmation of diagnosis and tissue adequacy for mandatory research studies

Patients must have 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

International Prognostic Index (IPI) of 2 or greater

Ejection fraction of >= 45% by either multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)

Absence of 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, 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

Absolute neutrophil count (ANC) >= 1500

Platelets (PLT) >= 100,000

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

Alkaline (Alk.) phosphatase =< 3 x ULN unless evidence of the direct liver involvement by lymphoma – then =< 5 x ULN

Aspartate aminotransferase (AST) =< 3 x ULN unless evidence of the direct liver involvement by lymphoma – then =< 5 x ULN

Creatinine =< 2 x ULN or creatinine clearance (CrCl) > 30 ml/min

Women must not be pregnant or breast-feeding

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 prior to and again within 24 hours of starting lenalidomide and 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 she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 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)

Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

National Cancer Institute

  • National Cancer Institute
Grzegorz S. Nowakowski, Principal Investigator

Trial Sites

U.S.A.

Colorado
Denver

Colorado Cancer Research Program NCORP

Keren Sturtz
Ph: 888-785-6789

Keren Sturtz
Principal Investigator

Florida
Lakeland

The Watson Clinic

Galina Vugman
Ph: 863-603-4720
Email: gvugman@watsonclinic.com

Galina Vugman
Principal Investigator

Idaho
Boise

Saint Alphonsus Cancer Care Center-Boise

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Illinois
Galesburg

Illinois CancerCare-Galesburg Cottage Plaza Office

Nguyet Anh Le-Lindqwister
Ph: 800-793-2262

Nguyet Anh Le-Lindqwister
Principal Investigator

Indiana
South Bend

Northern Indiana Cancer Research Consortium

Jose A. Bufill
Ph: 574-237-1328

Jose A. Bufill
Principal Investigator

Louisiana
Baton Rouge

Ochsner Health Center-Summa

Robert Van Buren Emmons
Ph: 888-562-4763

Robert Van Buren Emmons
Principal Investigator

Kenner

Ochsner Medical Center Kenner

Robert Van Buren Emmons
Ph: 888-562-4763

Robert Van Buren Emmons
Principal Investigator

New Orleans

Ochsner Medical Center Jefferson

Robert Van Buren Emmons
Ph: 888-562-4763

Robert Van Buren Emmons
Principal Investigator

Michigan
Ann Arbor

Saint Joseph Mercy Hospital

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Dearborn

Beaumont Hospital-Dearborn

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Detroit

Saint John Hospital and Medical Center

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Flint

Genesys Hurley Cancer Institute

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Jackson

Allegiance Health

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Livonia

Saint Mary Mercy Hospital

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Pontiac

Saint Joseph Mercy Oakland

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Saginaw

Saint Mary's of Michigan

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Warren

Saint John Macomb-Oakland Hospital

Christopher M. Reynolds
Ph: 734-712-4673
Email: christopher_reynolds@ihacares.com

Christopher M. Reynolds
Principal Investigator

Nevada
Las Vegas

Nevada Cancer Research Foundation CCOP

John Allan Ellerton
Ph: 702-384-0013

John Allan Ellerton
Principal Investigator

New Jersey
Livingston

Saint Barnabas Medical Center

Miguel A. Conde
Ph: 973-322-2470
Email: mconde@barnabashealth.org

Miguel A. Conde
Principal Investigator

Ohio
Akron

Akron General Medical Center

Esther Hoogland Rehmus
Ph: 330-344-6348

Esther Hoogland Rehmus
Principal Investigator

Maumee

Toledo Clinic Cancer Centers-Maumee

Rex B. Mowat
Ph: 800-444-3561

Rex B. Mowat
Principal Investigator

Toledo

Toledo Clinic Cancer Centers-Toledo

Rex B. Mowat
Ph: 800-444-3561

Rex B. Mowat
Principal Investigator

South Dakota
Sioux Falls

Avera Cancer Institute

Amy K. Krie
Ph: 888-634-7268
Email: oncregulatory@avera.org

Amy K. Krie
Principal Investigator

Virginia
Fishersville

Augusta Health Cancer Center

Zuhair Ghanem
Ph: 540-245-7106

Zuhair Ghanem
Principal Investigator

Wisconsin
Milwaukee

Aurora Cancer Care-Milwaukee South

Rubina Qamar
Ph: 888-709-2080

Rubina Qamar
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01856192

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.