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

NCT01029730 | Completed Phase 2 Results

• 1 other identifier: SCRI LYM 66
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 20

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.

Conditions

Lymphoma

Keywords

Low grade lymphoma; Previously untreated lymphoma; Lymphoma first line; bendamustine; Treanda; bortezomib; Velcade; rituximab; Rituxan

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  Percentage of patients experiencing a complete response (CR) per RECIST. CR = disappearance of all target lesions.

  18 months

Secondary Outcomes (3)

• Overall Response Rate

  At 3 and 6 months during treatment, then 6 months post-treatment.

• Median Progression-free Survival

  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.

• Number of Participants With Adverse Events as a Measure of Safety.

  Days 1,8, and 15 of each 28-day cycle for 6 months, then every 3 months for a year, projected 2 years.

Study Arms (1)

Bendamustine/Bortezomib/Rituximab

EXPERIMENTAL

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.

Drug: Bendamustine; Drug: Bortezomib; Drug: Rituximab

Interventions

Bendamustine DRUG

Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles

Also known as: TREANDA®

Bendamustine/Bortezomib/Rituximab

Bortezomib DRUG

Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles

Also known as: VELCADE®

Bendamustine/Bortezomib/Rituximab

Rituximab DRUG

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

Also known as: Rituxan®

Bendamustine/Bortezomib/Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Cephalon: collaborator

Study Sites (20)

NEA Baptist Clinic

Jonesboro, Arkansas, 72401, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Hematology Oncology of the North Shore

Skokie, Illinois, 60076, United States

Location

Providence Medical Group

Terre Haute, Indiana, 47802, United States

Location

Baptist Hospital East

Louisville, Kentucky, 40207, United States

Location

Hematology Oncology Clinic, LLP

Baton Rouge, Louisiana, 70806, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

National Capital Clinical Research Consortium

Bethesda, Maryland, 20817, United States

Location

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

St. Louis Cancer Care

Chesterfield, Missouri, 63017, United States

Location

Portsmouth Regional Hospital

Portsmouth, New Hampshire, 03801, United States

Location

Hematology-Oncology Associates of Northern NJ

Morristown, New Jersey, 07960, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Cancer Centers of Southwest Oklahoma

Lawton, Oklahoma, 73505, United States

Location

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Schiffler Cancer Center

Wheeling, West Virginia, 26003, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin

Interventions

Bendamustine Hydrochloride; Bortezomib; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: John D Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• Ian W. Flinn, MD, PhD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2009
• First Posted: December 10, 2009
• Study Start: March 1, 2010
• Primary Completion: October 1, 2014
• Study Completion: July 1, 2016
• Last Updated: August 19, 2016
• Results First Posted: December 28, 2015

Record last verified: 2016-07

Locations

US (20)