Trial of VELCADE and Rituxan as Front-line Tx for Low-grade NHL

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Robert H. Lurie Cancer Center
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT00369707
First received: August 24, 2006
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with rituximab may kill more cancer cells.

This phase II trial is studying how well giving bortezomib together with rituximab works as first-line therapy in treating patients with low-grade B-cell non-Hodgkin's lymphoma.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: Rituximab
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Combination Bortezomib and Rituximab as Front-line Therapy for Low-grade Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Overall response rate (complete response and partial response) [ Time Frame: baseline, every 2 months at the completion of cycles 1, 2 and 3 and 2 months after cycle 3 completion and then every 6 mo for 2 yrs ] [ Designated as safety issue: No ]
    The primary objective of this study is to assess the overall response rate (complete response [CR] plus partial response [PR]) after 3 cycles of bortezomib/rituximab induction therapy for patients with previously untreated low-grade, B-cell NHL.


Secondary Outcome Measures:
  • Overall response rate after 1 course of induction therapy [ Time Frame: every 2 months at the completion of cycles 1, 2 and 3 and 2 months after cycle 3 completion ] [ Designated as safety issue: No ]
    Overall response rate (ORR) after 1 cycle of bortezomib/rituximab induction therapy.

  • Overall response rate after completion of maintenance therapy [ Time Frame: every 2 months at the completion of cycles 1, 2 and 3 and 2 months after cycle 3 completion ] [ Designated as safety issue: No ]
    Overall response rate at completion of bortezomib/rituximab maintenance therapy.

  • Duration of response [ Time Frame: every 2 months for 8 months then every 6 mos for 2 yrs ] [ Designated as safety issue: No ]
    Duration of response, Time to progression, Progression free survival, and Time to treatment failure.

  • Safety and tolerability [ Time Frame: Day 1 of each cycle and at the completion of cycles 1 and 3 ] [ Designated as safety issue: Yes ]
    Assess the safety and tolerance of bortezomib/rituximab as induction and maintenance therapy.

  • Tissue evaluation [ Time Frame: baseline and at response assessment 1, 2 and 3 ] [ Designated as safety issue: No ]
    Tissue microarray analysis from paraffin embedded tissue, gene expression profiling from frozen tissue (both from initial node biopsy collected/stored) and whole blood analysis of FCγR polymorphism

  • Correlation of tumor burden [ Time Frame: End of study ] [ Designated as safety issue: No ]
    Correlation of tumor burden according to Groupe D'Etude des Lymphomes Follicularies (GELF) with recently developed Follicular Lymphoma International Prognostic Index (FLIPI) prognostic index.


Estimated Enrollment: 43
Study Start Date: August 2006
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib and Rituximab
On days 1, 8, 15 and 22 of the 1st cycle, bortezomib will be administered intravenously (through a vein) over 3-5 seconds followed by an intravenous infusion of rituximab. How long it will take to infuse the dose of rituximab is dependent upon your weight and how well you tolerate the infusion; it is estimated this first infusion may take between 3-4 hours. During subsequent cycles, bortezomib will again be given on days 1, 8, 15 and 22. However, rituximab will only be given on day 1 of each cycle.
Drug: Rituximab
On days 1, 8, 15 and 22 of the 1st cycle, bortezomib will be administered intravenously (through a vein) over 3-5 seconds followed by an intravenous infusion of rituximab. How long it will take to infuse the dose of rituximab is dependent upon your weight and how well you tolerate the infusion; it is estimated this first infusion may take between 3-4 hours. During subsequent cycles, bortezomib will again be given on days 1, 8, 15 and 22. However, rituximab will only be given on day 1 of each cycle.
Other Name: Rituxan
Drug: bortezomib
On days 1, 8, 15 and 22 of the 1st cycle, bortezomib will be administered intravenously (through a vein) over 3-5 seconds followed by an intravenous infusion of rituximab. How long it will take to infuse the dose of rituximab is dependent upon your weight and how well you tolerate the infusion; it is estimated this first infusion may take between 3-4 hours. During subsequent cycles, bortezomib will again be given on days 1, 8, 15 and 22. However, rituximab will only be given on day 1 of each cycle.
Other Name: Velcade, PS-341

Detailed Description:

This is a multicenter, prospective study.

  • Induction therapy: Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 of all subsequent courses. Treatment repeats every 35 days for 3 courses. Patients achieving a complete response, partial response, or stable disease proceed to maintenance therapy.
  • Maintenance therapy: Beginning 6-8 weeks after induction therapy, patients receive bortezomib IV over 3-5 seconds and rituximab IV on day 1. Treatment repeats every 60 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected at baseline and periodically during study treatment.

After completion of study therapy, patients are followed every 3 months for 2 years.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed low-grade B-lymphocyte non-Hodgkins lymphoma
  • Life expectancy > 12 months

Exclusion Criteria:

  • No known history of HIV infection
  • No other active infection
  • No peripheral neuropathy ≥ grade 2 within the past 14 days
  • No uncontrolled hypertension
  • None of the following cardiac conditions:

    • Myocardial infarction within the past 6 months
    • No heart failure
    • Uncontrolled angina
    • Severe uncontrolled ventricular arrhythmias
    • Electrocardiographic evidence of acute ischemia
    • Active conduction system abnormalities
  • No serious medical or psychiatric illness that would preclude study compliance
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior therapy for non-Hodgkins lymphoma
  • No prior bortezomib or rituximab
  • At least 3 weeks since prior chemotherapy, radiation therapy, immunotherapy, systemic anticancer biologic therapy, or anticancer hormonal therapy
  • At least 2 weeks since prior investigational drugs
  • No other concurrent systemic cytotoxic chemotherapy or investigational agents + No leukemia
  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: NCT00369707

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
United States, Illinois
Hematology-Oncology Associates of Illinois
Chicago, Illinois, United States, 60611-2998
Northwestern University
Chicago, Illinois, United States, 60611
United States, Pennsylvania
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
Northwestern University
Robert H. Lurie Cancer Center
Investigators
Principal Investigator: Andrew M. Evens, DO, MS Northwestern University
  More Information

Additional Information:
No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00369707     History of Changes
Other Study ID Numbers: NU 06H1, STU00005335
Study First Received: August 24, 2006
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Northwestern University:
Non-Hodgkin's Lymphoma

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

ClinicalTrials.gov processed this record on August 20, 2014