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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01856192
First received: May 14, 2013
Last updated: July 22, 2014
Last verified: May 2014

May 14, 2013
July 22, 2014
August 2013
May 2015   (final data collection date for primary outcome measure)
PFS [ Time Frame: Time from randomization to the earliest of documented disease progression, new primaries of the same type or death without progression, assessed up to 10 years ] [ Designated as safety issue: No ]
The primary analysis of PFS will be performed including all randomized eligible patients using a one-sided log-rank test stratified on IPI (2-3 vs. 4-5), age (< 60 years vs >= 60 years) and molecular subtype (germinal center B-cell type [GCB] vs. activated B-cell type [ABC]). Cox proportional hazards models will be used to assess possible effects of baseline clinical and biological characteristics on outcome, including age, gender, disease stage, and IPI. Treatment and covariate interactions will also be examined.
PFS [ Time Frame: Time from randomization to the earliest of documented disease progression, new primaries of the same type or death without progression, assessed up to 10 years ] [ Designated as safety issue: No ]
The primary analysis of PFS will be performed including all randomized eligible patients using a one-sided log-rank test stratified on IPI (2-3 vs. 4-5), age (<60 years vs >= 60 years) and molecular subtype (germinal Center B-cell type [GCB] vs. activated B-cell type [ABC]). Cox proportional hazards models will be used to assess possible effects of baseline clinical and biological characteristics on outcome, including age, gender, disease stage, and IPI. Treatment and covariate interactions will also be examined.
Complete list of historical versions of study NCT01856192 on ClinicalTrials.gov Archive Site
  • Overall RR based on PET-CT scan [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The comparison of RR between two arms will be performed with Cochran-Mantel-Haenszel (CMH) test, stratified on IPI (2-3 vs 4-5), age (< 60 yrs vs >= 60 yrs) and molecular subtype (GCB vs. ABC). Exploratory logistic regression will be used to assess possible effects of baseline clinical and biological characteristics on outcome, including age, gender, disease stage, and IPI. Treatment and covariate interactions will also be examined.
  • CR rate based on PET-CT scan [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The comparison of CR between two arms will be performed with CMH test, stratified on IPI (2-3 vs 4-5), age (< 60 yrs vs >= 60 yrs) and molecular subtype (GCB vs. ABC). Exploratory logistic regression will be used to assess possible effects of baseline clinical and biological characteristics on outcome, including age, gender, disease stage, and IPI. Treatment and covariate interactions will also be examined.
  • OS [ Time Frame: Time from randomization until death due to any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    The method of Kaplan and Meier will be used to estimate OS, and stratified log-rank test will be used to compare OS between two arms.
  • Overall RR based on PET-CT scan [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The comparison of RR between two arms will be performed with Cochran-Mantel-Haenszel (CMH) test, stratified on IPI (2-3 vs 4-5), age (< 60 yrs vs ≥ 60 yrs) and molecular subtype (GCB vs. ABC). Exploratory logistic regression will be used to assess possible effects of baseline clinical and biological characteristics on outcome, including age, gender, disease stage, and IPI. Treatment and covariate interactions will also be examined.
  • CR rate based on PET-CT scan [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The comparison of CR between two arms will be performed with CMH test, stratified on IPI (2-3 vs 4-5), age (< 60 yrs vs ≥ 60 yrs) and molecular subtype (GCB vs. ABC). Exploratory logistic regression will be used to assess possible effects of baseline clinical and biological characteristics on outcome, including age, gender, disease stage, and IPI. Treatment and covariate interactions will also be examined.
  • OS [ Time Frame: Time from randomization until death due to any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    The method of Kaplan and Meier will be used to estimate OS, and stratified log-rank test will be used to compare OS between two arms.
  • Impact of DLBCL molecular subtype on outcome [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Relation between interim PET scan and study outcome [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
Not Provided
 
Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma
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

This randomized phase II trial studies how well rituximab and combination chemotherapy with or without lenalidomide works in treating patients with newly diagnosed stage II-IV diffuse large B cell lymphoma. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. 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 or by stopping them from dividing. 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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Contiguous Stage II Adult Diffuse Large Cell Lymphoma
  • Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
  • Stage III Adult Diffuse Large Cell Lymphoma
  • Stage IV Adult Diffuse Large Cell Lymphoma
  • Drug: lenalidomide
    Given PO
    Other Names:
    • CC-5013
    • IMiD-1
    • Revlimid
  • Biological: rituximab
    Given IV
    Other Names:
    • IDEC-C2B8
    • IDEC-C2B8 monoclonal antibody
    • Mabthera
    • MOAB IDEC-C2B8
    • Rituxan
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Drug: prednisone
    Given PO
    Other Names:
    • DeCortin
    • Deltra
  • Other: laboratory biomarker analysis
    Correlative studies
  • Procedure: positron emission tomography
    Correlative studies
    Other Names:
    • FDG-PET
    • PET
    • PET scan
    • tomography, emission computed
  • Experimental: Arm A (rituximab, combination chemotherapy, lenalidomide)
    Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, prednisone 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.
    Interventions:
    • Drug: lenalidomide
    • Biological: rituximab
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: vincristine sulfate
    • Drug: prednisone
    • Other: laboratory biomarker analysis
    • Procedure: positron emission tomography
  • Active Comparator: Arm B (rituximab, combination chemotherapy)
    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.
    Interventions:
    • Biological: rituximab
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: vincristine sulfate
    • Drug: prednisone
    • Other: laboratory biomarker analysis
    • Procedure: positron emission tomography
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
300
Not Provided
May 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed DLBCL expressing cluster of differentiation (CD)20 antigen (Journal of Clinical Oncology [J Clin Oncol] 17[4]:1244-53, 1999); 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 frequently are treated with abbreviated chemoimmunotherapy followed by involved field radiation and may be eligible for other protocols and are thus 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
Both
18 Years and older
No
United States
 
NCT01856192
NCI-2013-00959, NCI-2013-00959, ECOG-E1412, E1412, E1412, U10CA180820, U10CA021115
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Grzegorz Nowakowski ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP