Trial of Bendamustine, Bortezomib, and Rituximab in Patients With Previously Untreated Low Grade Lymphoma

Tracking Information
First Submitted Date ICMJE	December 8, 2009
First Posted Date ICMJE	December 10, 2009
Results First Submitted Date	November 19, 2015
Results First Posted Date	December 28, 2015
Last Update Posted Date	August 19, 2016
Study Start Date ICMJE	March 2010
Actual Primary Completion Date	October 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 19, 2015)	Complete Response Rate [ Time Frame: 18 months ]; Percentage of patients experiencing a complete response (CR) per RECIST. CR = disappearance of all target lesions.
Original Primary Outcome Measures ICMJE; (submitted: December 9, 2009)	To determine the complete response rate in patients with previously untreated low grade lymphoma following treatment with bendamustine/bortezomib/rituximab. [ Time Frame: 18 months ]
Change History	Complete list of historical versions of study NCT01029730 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 2, 2016)	Overall Response Rate [ Time Frame: At 3 and 6 months during treatment, then 6 months post-treatment. ]The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.; Median Progression-free Survival [ Time Frame: at 3 and 6 months, then every 3 months post-treatment for 1 year and every 6 months thereafter until disease progression; projected 2 years. ]The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.; Number of Participants With Adverse Events as a Measure of Safety. [ Time Frame: Days 1,8, and 15 of each 28-day cycle for 6 months, then every 3 months for a year, projected 2 years. ]Toxicity grades will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. Includes adverse events occurring in >1 patient
Original Secondary Outcome Measures ICMJE; (submitted: December 9, 2009)	To assess overall response rate (ORR) in patients with previously untreated low grade lymphoma following treatment with bendamustine/bortezomib/rituximab. [ Time Frame: 18 months ]; To assess progression-free survival (PFS) of patients with previously untreated low grade lymphoma following treatment with bendamustine/bortezomib/rituximab. [ Time Frame: 18 months ]; To characterize the toxicity of bendamustine/bortezomib/rituximab in patients with previously untreated low grade lymphoma. [ Time Frame: 18 months ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Trial of Bendamustine, Bortezomib, and Rituximab in Patients With Previously Untreated Low Grade Lymphoma
Official Title ICMJE	Phase II Trial of Bendamustine, Bortezomib, and Rituximab in Patients With Previously Untreated Low Grade Lymphoma
Brief Summary	The goal of this multi-center Phase II study is to add bortezomib to the highly active regimen of bendamustine and rituximab. In this study, bortezomib will be administered on a weekly schedule (Days 1, 8, 15) and will be added to bendamustine/rituximab given in 4-week cycles. This combination uses the standard bendamustine dosing schedule, and is more convenient than the 5-week regimen of these 3 drugs currently being studied.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Lymphoma
Intervention ICMJE	Drug: Bendamustine Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles Other Name: TREANDA®; Drug: Bortezomib Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles Other Name: VELCADE®; Drug: Rituximab Rituximab, Cycle 1: 375 mg/m2 given IV on Day 1, Day 8, and Day 15 Rituximab, Cycles 2-6: 375 mg/m2 given IV on Day 1 Other Name: Rituxan®
Study Arms	Experimental: Bendamustine/Bortezomib/Rituximab; Treatment for all patients will be given in cycles of 28 days (4 weeks). All patients will receive treatment with bendamustine, bortezomib, and rituximab for a maximum of 6 cycles. Rituximab should be administered first.; Interventions: Drug: Bendamustine; Drug: Bortezomib; Drug: Rituximab
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 9, 2009)	55
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	July 2016
Actual Primary Completion Date	October 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Histologically-confirmed indolent lymphoma by the World Health Organization (WHO) classification. The biopsy must fulfill one of the following criteria: Follicular lymphoma, grade 1 or 2 Marginal zone lymphoma Small lymphocytic lymphoma (circulating lymphocyte count must be <5,000) Lymphoplasmacytic lymphoma; At least one of the following criteria must be met: Presence of any symptoms related to lymphoma. These can include classic B-symptoms (fever [>38°C] of unclear etiology, night sweats, weight loss of greater than 10% within the prior 6 months) or other lymphoma-related symptoms (fatigue, pain, etc.). Large tumor mass (bulky disease) characterized by lymphomas with a diameter of more than 3 cm in three or more regions or by a lymphoma with a diameter >7 cm in one 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; The lymph node biopsy or other lymphoma pathology specimen has CD20+ B-cells.; Ann-Arbor Stage 2 (non-contiguous), 3, or 4 disease.; No previous systemic treatment for lymphoma. Patients may have had a single course of radiation therapy to a limited field (i.e., not exceeding two adjacent lymph node regions).; The patient has bidimensionally measurable disease with at least 1 lesion measuring ≥2.0 cm in a single dimension, and the field was not previously radiated.; An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.; Adequate hematologic function ≤7 days prior to start of study treatment: Hemoglobin ≥10.0 g/dl Absolute neutrophil count (ANC) ≥1000/µL Platelet count ≥75,000/µL. If low counts are attributable to bone marrow infiltration or hypersplenism due to lymphoma, ANC must be ≥750/µL and platelets ≥50,000/µL.; Calculated or measured creatinine clearance ≥30 mL/min ≤7 days of study enrollment (using Cockcroft-Gault method).; Adequate hepatic function (≤2.5 x upper limit of normal [ULN] for alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase and total bilirubin within normal limits).; Patients must be ≥18 years of age.; Women of childbearing potential must agree to use a medically acceptable method of birth control (e.g., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 12 months after their last dose of rituximab. Men must use an acceptable method/form of contraception for the duration of treatment and for 3 months after the end of treatment.; Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry. Exclusion Criteria: The patient has chronic lymphocytic leukemia.; The patient has transformed lymphoma.; History of, or clinically apparent, central nervous system (CNS) lymphoma or leptomeningeal lymphoma.; The patient has received corticosteroids for treatment of lymphoma. Chronic, low-dose corticosteroids (e.g., prednisone ≤20 mg/day) are allowed for treatment uses other than lymphoma or complications of lymphoma.; Peripheral neuropathy ≥ CTCAE v3.0 grade 2, ≤14 days of study enrollment.; Myocardial infarction ≤6 months prior to study enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, ECG abnormalities at screening must be documented as not medically relevant.; History of solid organ transplantation, or post-transplant lymphoproliferative disorder.; Patients with known history of hepatitis B or hepatitis C infection. Hepatitis B surface antigen must be tested.; The patient has known human immunodeficiency virus (HIV) infection.; Active, clinically serious infection > grade 2. Patients may be eligible upon resolution of the infection.; Female patient is pregnant or breast-feeding. Confirmation that female patients of childbearing potential are not pregnant must be established by a negative serum pregnancy test ≤7 days prior to the start of treatment.; Known hypersensitivity to bendamustine, bortezomib, boron, mannitol, or rituximab.; Concomitant active malignancy requiring therapy.; Diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.; Treatment with other investigational agents ≤14 days prior to study enrollment.; Any other disease(s), psychiatric condition, metabolic dysfunction, or findings from a physical examination or clinical laboratory test result that would cause reasonable suspicion of a disease or condition, that contraindicates the use of study drugs, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the patient inappropriate for this study.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01029730
Other Study ID Numbers ICMJE	SCRI LYM 66
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	SCRI Development Innovations, LLC
Study Sponsor ICMJE	SCRI Development Innovations, LLC
Collaborators ICMJE	Millennium Pharmaceuticals, Inc.; Cephalon
Investigators ICMJE	Study Chair: Ian W. Flinn, MD, PhD SCRI Development Innovations, LLC
PRS Account	SCRI Development Innovations, LLC
Verification Date	July 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP