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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Cephalon
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01029730
First received: December 8, 2009
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

The goal of this 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. This trial will be conducted at multiple study sites by the Sarah Cannon Research Institute (SCRI) Oncology Research Consortium.


Condition Intervention Phase
Lymphoma
Drug: Bendamustine
Drug: Bortezomib
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Bendamustine, Bortezomib, and Rituximab in Patients With Previously Untreated Low Grade Lymphoma

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • To determine the complete response rate in patients with previously untreated low grade lymphoma following treatment with bendamustine/bortezomib/rituximab. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess overall response rate (ORR) in patients with previously untreated low grade lymphoma following treatment with bendamustine/bortezomib/rituximab. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To assess progression-free survival (PFS) of patients with previously untreated low grade lymphoma following treatment with bendamustine/bortezomib/rituximab. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To characterize the toxicity of bendamustine/bortezomib/rituximab in patients with previously untreated low grade lymphoma. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 55
Study Start Date: January 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Bendamustine, Bortezomib, and Rituximab
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®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. 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
  3. The lymph node biopsy or other lymphoma pathology specimen has CD20+ B-cells.
  4. Ann-Arbor Stage 2 (non-contiguous), 3, or 4 disease.
  5. 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).
  6. 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.
  7. An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
  8. 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.
  9. Calculated or measured creatinine clearance ≥30 mL/min ≤7 days of study enrollment (using Cockcroft-Gault method).
  10. 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).
  11. Patients must be ≥18 years of age.
  12. 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.
  13. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Exclusion Criteria:

  1. The patient has chronic lymphocytic leukemia.
  2. The patient has transformed lymphoma.
  3. History of, or clinically apparent, central nervous system (CNS) lymphoma or leptomeningeal lymphoma.
  4. 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.
  5. Peripheral neuropathy ≥ CTCAE v3.0 grade 2, ≤14 days of study enrollment.
  6. 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.
  7. History of solid organ transplantation, or post-transplant lymphoproliferative disorder.
  8. Patients with known history of hepatitis B or hepatitis C infection. Hepatitis B surface antigen must be tested.
  9. The patient has known human immunodeficiency virus (HIV) infection.
  10. Active, clinically serious infection > grade 2. Patients may be eligible upon resolution of the infection.
  11. 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.
  12. Known hypersensitivity to bendamustine, bortezomib, boron, mannitol, or rituximab.
  13. Concomitant active malignancy requiring therapy.
  14. 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.
  15. Treatment with other investigational agents ≤14 days prior to study enrollment.
  16. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01029730

  Hide Study Locations
Locations
United States, Arkansas
NEA Baptist Clinic
Jonesboro, Arkansas, United States, 72401
United States, Florida
Holy Cross Hospital
Ft. Lauderdale, Florida, United States, 33308
Florida Cancer Specialists
Ft. Myers, Florida, United States, 33916
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Illinois
Hematology Oncology of the North Shore
Skokie, Illinois, United States, 60076
United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
United States, Kentucky
Baptist Hospital East
Louisville, Kentucky, United States, 40207
United States, Louisiana
Hematology Oncology Clinic, LLP
Baton Rouge, Louisiana, United States, 70806
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
National Capital Clinical Research Consortium
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
United States, New Hampshire
Portsmouth Regional Hospital
Portsmouth, New Hampshire, United States, 03801
United States, New Jersey
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07960
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, Oklahoma
Cancer Centers of Southwest Oklahoma
Lawton, Oklahoma, United States, 73505
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
United States, Texas
Leading Edge Research, P.A.
Dallas, Texas, United States, 75243
The Center for Cancer and Blood Disorders
Fort Worth, Texas, United States, 76104
United States, West Virginia
Schiffler Cancer Center
Wheeling, West Virginia, United States, 26003
Sponsors and Collaborators
SCRI Development Innovations, LLC
Millennium Pharmaceuticals, Inc.
Cephalon
Investigators
Study Chair: Ian W. Flinn, MD, PhD SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01029730     History of Changes
Other Study ID Numbers: SCRI LYM 66
Study First Received: December 8, 2009
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Low grade lymphoma
Previously untreated lymphoma
Lymphoma first line
bendamustine
Treanda
bortezomib
Velcade
rituximab
Rituxan

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Nitrogen Mustard Compounds
Rituximab
Bortezomib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 19, 2014