Overview

This trial is active, not recruiting.

Condition lymphoma
Treatments bendamustine, bortezomib, rituximab
Phase phase 2
Targets CD20, proteasome
Sponsor SCRI Development Innovations, LLC
Collaborator Millennium Pharmaceuticals, Inc.
Start date March 2010
End date October 2014
Trial size 55 participants
Trial identifier NCT01029730, SCRI LYM 66

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(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.
bendamustine TREANDA®
Bendamustine: 90 mg/m2 Days 1 and 2 of 6, 28-day cycles
bortezomib VELCADE®
Bortezomib: 1.6 mg/m2 given IV on Day 1, Day 8, and Day 15 of 6, 28-day cycles
rituximab Rituxan®
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

Primary Outcomes

Measure
Complete Response Rate
time frame: 18 months

Secondary Outcomes

Measure
Overall Response Rate
time frame: At 3 and 6 months during treatment, then 6 months post-treatment.
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.
Frequency of adverse events and their severity 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.

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

Official title Phase II Trial of Bendamustine, Bortezomib, and Rituximab in Patients With Previously Untreated Low Grade Lymphoma
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by SCRI Development Innovations, LLC.