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An Open-Label, Randomized, Parallel-Group Study of Bendamustine Hydrochloride and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in the First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL).

Phase 3
Active, not recruiting
Conditions
on-Hodgkin's Lymphoma
Non-Hodgkin's Lymphoma
Cancer - Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer - Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Registration Number
ACTRN12610000445077
Lead Sponsor
Cephalon Inc
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Active, not recruiting
Sex
All
Target Recruitment
436
Inclusion Criteria

(a) Histopathologic confirmation of 1 of the following CD20+ B-cell non-Hodgkin’s lymphomas (World Health Organization [WHO]/Revised European American Classification of Lymphoid Neoplasms [REAL] classifications described below). Tissue diagnostic
procedures must be performed within 6 months of study entry and with biopsy material available for review:
* follicular lymphoma (grade 1 or 2)
* immunoplasmacytoma/immunocytoma (Waldenstrom’s macroglobulinemia)
* splenic marginal zone B-cell lymphoma
* extra-nodal marginal zone lymphoma of mucosa associated lymphoid tumor (MALT) type
* nodal marginal zone B-cell lymphoma
* mantle cell lymphoma

(b) The patient meets 1 of the following need-for–treatment criteria with the exception of mantle cell lymphoma, for which treatment is always indicated:
* presence of at least 1 of the following B-symptoms:
** fever (>38 degrees C) of unclear etiology
** night sweats
** weight loss of greater than 10% within the prior 6 months
* large tumor mass (bulky disease) characterized by lymphomas with a diameter of more than 3 cm in 3 or more regions or by a lymphoma with a diameter of more than 7 cm in 1 region
* presence of lymphoma-related complications, including narrowing of ureters or bile ducts, tumor-related compression of a vital organ, lymphoma induced pain, cytopenias related to lymphoma/leukemia, splenomegaly, pleural effusions, or ascites
* hyperviscosity syndrome due to monoclonal gammopathy

(c) The patient has CD20 positive B cells in the lymph node biopsy or other lymphoma pathology specimen.

(e) The patient was not previously treated. Patients on watch and wait” may enter the study if a recent biopsy (obtained within the last 6 months) is obtainable.

(f) The patient has adequate hematologic function (unless abnormalities are related to lymphoma infiltration of the bone marrow or hypersplenism due to lymphoma) within 30 days prior to start of study drug as evidenced by the following:
* hemoglobin of 10.0 g/dl or greater
* absolute neutrophil count (ANC) of 1.5 x 109/L or greater
* platelet count of 100 x109/L or greater

(g) The patient has bidimensionally measurable disease with at least 1 lesion measuring 2.0 cm or more in a single dimension, and the field was not previously radiated.

(h) The patient is able to provide written informed consent.

(i) The patient is 18 years of age or older at the time of informed consent.

(j) The patient has an Eastern Cooperative Oncology Group (ECOG) performance status 2 or less.

(k) The patient has an estimated life expectancy of at least 6 months.

(l) The patient has serum creatinine of 2.0 mg/dL or less, or Creatinine Clearance of 50 mL/min or more based on the Cockcroft-Gault method or from a 24-hour urine collection.

(m) The patient has adequate hepatic organ function (less than or equal to 2.5 times the upper limit of normal for alanine aminotransferase [ALT], asparate aminotransferase [AST], and alkaline phosphatase and total bilirubin within normal limits).

(n) The patient has left ventricular ejection fraction (LVEF) 50% or greater by Multiple Uptake Gated Aquisition (MUGA) scan or Echocardiogram (ECHO) within 30 days prior to start of study drug treatment for any patient who will be treated with R-CHOP.

(o) Women of childbearing potential (not surgically sterile or at least 12 months naturally postmenopausal) must use a medically accepted method of contraception and must

Exclusion Criteria

(a) The patient has chronic lymphocytic leukemia, small lymphocytic lymphoma, or grade 3 follicular lymphoma.

(b) The patient has transformed disease. Specifically, bone marrow blasts are permitted, however, transformed disease indicating leukemic involvement is not permitted.

(c) The patient has the presence or history of central nervous system (CNS) involvement or leptomeningeal lymphoma.

(d) The patient had prior treatment for NHL except for a single course of locally delimited radiation therapy (radiation field not exceeding 2 adjacent lymph node regions).

(e) The patient has had an active malignancy, other than NHL, within the past 3 years except for localized prostate cancer treated with hormone therapy, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer that has been definitively treated.

(f) The patient has New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiographic evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months. (Prior to study entry, Electrocardiogram (ECG) abnormalities at screening must be documented by the investigator as not medically relevant).

(g) The patient has a known human immunodeficiency virus (HIV) infection.

(h) The patient has active hepatitis B or hepatitis C infection. Hepatitis B surface antigen must be tested, otherwise the determination of active hepatitis B or C is left
to the investigator.

(i) The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)

(j) The patient has received corticosteroids for treatment of lymphoma within 28 days of study entry. Chronically administered low-dose corticosteroids (eg, prednisone
=20 mg/day) for indications other than lymphoma or lymphoma-related complications are permitted.

(k) The patient has any serious uncontrolled, medical or psychological disorder that would impair the ability of the patient to receive protocol therapy.

(l) The patient has any condition which places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data.

(m) The patient has received other investigational agent within 28 days of study entry.

(n) The patient has known hypersensitivity to bendamustine, mannitol, or other study-related drugs.

(o) The patient has Ann Arbor stage I disease.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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