Phase I/II Trial of VELCADE Plus Zevalin in Patients With Relapsed or Refractory Follicular Lymphoma

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:
NCT00372905
First received: September 6, 2006
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving bortezomib together with rituximab and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.

This phase I/II trial is studying the side effects and best dose of bortezomib when given together with rituximab and yttrium Y 90 ibritumomab tiuxetan and to see how well they work in treating patients with relapsed or refractory follicular non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Drug: rituximab
Drug: bortezomib
Drug: Ibritumomab tiuxetan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Combined Weekly Bortezomib (VELCADE®) and Y-90-Ibritumomab Tiuxetan (Zevalin) in Patients With Relapsed or Refractory Follicular Lymphoma and Transformed Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Maximum tolerated dose and tolerability of bortezomib combined with Y-90-Ibritumomab Tiuxetan [ Time Frame: Baseline, days 1, 8, 15, 22 of induction, days 36 and 50 of recovery, days 1, 8, 15 of consolidation cycle, 4 weeks after completion of treatment, every 3 mo for one year, every 6 mo for second year, once a year thereafter ] [ Designated as safety issue: Yes ]
    To determine the maximum tolerated dose (up to 1.6 mg/m2 ) of bortezomib combined with Y-90-Ibritumomab Tiuxetan in patients with relapsed and refractory follicular NHL and the tolerability of weekly bortezomib (three weeks out of four) following treatment with Y-90-Ibritumomab tiuxetan


Secondary Outcome Measures:
  • toxicity and efficacy of bortezomib combined with Y-90-ibritumomab tiuxetan [ Time Frame: Baseline, days 1, 8, 15, 22 of induction, days 36 and 50 of recovery, days 1, 8, 15 of consolidation cycle, 4 weeks after completion of treatment, every 3 mo for one year, every 6 mo for second year, once a year thereafter ] [ Designated as safety issue: Yes ]
    To further explore the toxicity and efficacy of bortezomib combined with Y-90-ibritumomab tiuxetan.


Estimated Enrollment: 24
Study Start Date: August 2006
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bortezomib, Ibritumomab tiuxetan, rituximab
Induction therapy will last 28 days. Bortezomib will be given on days 1, 8, 15, and 22. Rituximab will be given on days 8 and 15 along with 111-indium-ibritumomab tiuxetan. During consolidation therapy, Bortezomib will be given intravenously on days 1, 8, and 15 of each cycle for a maximum of 3 cycles. Rituximab or Y-90-ibritumomab tiuxetan will not be given during consolidation therapy.
Drug: rituximab
Induction therapy will last 28 days. Bortezomib will be given on days 1, 8, 15, and 22. Rituximab will be given on days 8 and 15 along with 111-indium-ibritumomab tiuxetan. During consolidation therapy, Bortezomib will be given intravenously on days 1, 8, and 15 of each cycle for a maximum of 3 cycles. Rituximab or Y-90-ibritumomab tiuxetan will not be given during consolidation therapy.
Other Name: Rituxan, IDEC-C2B8
Drug: bortezomib
Induction therapy will last 28 days. Bortezomib will be given on days 1, 8, 15, and 22. Rituximab will be given on days 8 and 15 along with 111-indium-ibritumomab tiuxetan. During consolidation therapy, Bortezomib will be given intravenously on days 1, 8, and 15 of each cycle for a maximum of 3 cycles. Rituximab or Y-90-ibritumomab tiuxetan will not be given during consolidation therapy.
Other Name: Velcade
Drug: Ibritumomab tiuxetan
Induction therapy will last 28 days. Bortezomib will be given on days 1, 8, 15, and 22. Rituximab will be given on days 8 and 15 along with 111-indium-ibritumomab tiuxetan. During consolidation therapy, Bortezomib will be given intravenously on days 1, 8, and 15 of each cycle for a maximum of 3 cycles. Rituximab or Y-90-ibritumomab tiuxetan will not be given during consolidation therapy.
Other Name: 111-indium-ibritumomab tiuxetan, Y-90-ibritumomab tiuxetan

Detailed Description:

This is a phase I, dose-escalation study of bortezomib followed by a phase II study.

Phase I:

- Induction therapy: Patients receive bortezomib IV over 3-5 seconds on days 1, 8, 15, and 22, rituximab IV on days 8 and 15, and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 15.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

- Consolidation therapy: Beginning 6-7 weeks after completing induction therapy, patients receive bortezomib IV over 3-5 seconds on days 1, 8, and 15. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Phase II: Patients receive induction therapy and consolidation therapy as in phase I, with bortezomib administered at the MTD determined in phase I.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

A total of 24 patients will be accrued for this study.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed follicular lymphoma
  • CD20+ at time of diagnosis or subsequently
  • More than 4 weeks since prior rituximab
  • More than 3 weeks since prior anticancer therapy (6 weeks for nitrosourea or mitomycin C)
  • More than 4 weeks since prior major surgery
  • More than 2 weeks since prior investigational drugs

Exclusion Criteria:

  • AIDS-related lymphoma
  • History or evidence of CNS involvement
  • Pregnant or nursing
  • known HIV positivity
  • serious medical or psychiatric illness that would preclude study participation
  • myocardial infarction within the past 6 months
  • congestive heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia or active conduction system abnormalities
  • known hypersensitivity to rituximab, bortezomib, boron, or mannitol
  • prior autologous or allogeneic stem cell transplantation
  • prior radioimmunoconjugate therapy or prior exposure to murine antibodies
  • prior external-beam irradiation to > 25% of active bone marrow
  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: NCT00372905

Locations
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Robert H. Lurie Cancer Center
Investigators
Principal Investigator: Jane Winter, MD Northwestern University
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00372905     History of Changes
Other Study ID Numbers: NU 05H9, STU00004871
Study First Received: September 6, 2006
Last Updated: September 4, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Northwestern University:
follicular lymphoma

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

ClinicalTrials.gov processed this record on October 19, 2014