Randomized Phase II Open Label Study of Lenalidomide R-CHOP (R2CHOP) vs RCHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) in Patients With Newly Diagnosed Diffuse Large B Cell Lymphoma
Rochester, Minn., Phoenix/Scottsdale, Ariz.
Trial status: Open for Enrollment
Why is this study being done?
I. Progression-free survival (PFS).
I. Response rate (RR). II. Complete remission (CR) rate as defined by positron emission tomography (PET)-computed tomography (CT) criteria.
III. Overall survival (OS).
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.
Who is eligible to participate?
- Histologically confirmed DLBCL expressing cluster of differentiation (CD)20 antigen; patients with transform lymphoma are excluded; 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 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 tumor tissue specimen from the initial diagnostic biopsy has been located and ready to ship to the Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) Pathology Coordinating Office within 30 days following registration; patients must have paraffin-embedded tumor specimen available for central pathology review and defined laboratory research studies; archived formalin fixed paraffin embedded (FFPE) tumor tissue block is required; if the block is unavailable for submission, please submit the below alternative requirements:
- One (1) hematoxylin & eosin (H&E) slide, and
- Twenty (20) 4 um unstained air-dried plus slides, and
- One (1) or more core punches (minimum of 4 mm diameter)
- International Prognostic Index (IPI) of 2 or greater
- ECOG performance status 0-2
- Patients must have measurable disease (at least 1 lesion of >= 1.5 cm in one diameter) as detected by CT or the CT images of the PET/CT
- Previously untreated and not receiving any other agent that would be considered as a treatment for the lymphoma
- 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
- 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
- Ejection fraction of >= 45% by either multi gated acquisition scan (MUGA) 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
- 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 history of deep vein thrombosis/embolism/thrombophilia may participate if they are on full anticoagulation during the treatment (warfarin or low molecular weight heparin at therapeutic doses)
- Patient must be able and willing to receive anticoagulation therapy with aspirin 325 mg daily prophylaxis, low molecular weight heparin, 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)
- Patient must be willing to provide informed written consent and to return to enrolling institution for follow-up
- 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