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

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ClinicalTrials.gov Identifier: NCT00372905
Recruitment Status : Terminated (Study was closed permanently before the accrual goal was met due to slow accrual)
First Posted : September 7, 2006
Results First Posted : October 17, 2018
Last Update Posted : September 4, 2019
Sponsor:
Collaborator:
Robert H. Lurie Cancer Center
Information provided by (Responsible Party):
Northwestern University

Brief Summary:

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 or disease Intervention/treatment Phase
Lymphoma Drug: rituximab Drug: bortezomib Drug: Ibritumomab tiuxetan Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : July 24, 2007
Actual Primary Completion Date : June 22, 2010
Actual Study Completion Date : July 8, 2013


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) and Tolerability of Bortezomib Combined With Y-90-Ibritumomab Tiuxetan Determined by Number of Dose Limiting Toxicities in a Cohort. [ Time Frame: During induction therapy, the first 28 days of treatment. ]

    To determine the MTD using a 3+3 dose escalating design. There will be 3 dose cohorts:1.0mg/m2,1.3mg/m2 and1.6 mg/m2. 3 patients will be enrolled at dose of 1.0mg/m2 bortezomib. If no dose limiting toxicities (DLTs) are seen in the first 3 patients then dose will be escalated to next level and 3 patients will be treated at that dose level. If a DLT is seen at any dose, then 3 more patients will be enrolled at that dose level. If 1 patient out of 6, experience a DLT then MTD will be determined to be at this dose level. If 2 or more DLTs are seen in first 3 patients at that dose, then MTD will be one dose lower to the level where the DLTs were experienced.

    DLTs were defined using the National Cancer Institute Common Toxicity Criteria Version 3.0.

    DLTs=grade 3 nausea, vomiting, diarrhea or ileus more than 96h; grade 4 nausea, vomiting, diarrhea or ileus,neuropathic pain, peripheral sensory neuropathy, neutropenia, thrombocytopenia.



Secondary Outcome Measures :
  1. Number of Patients With Adverse Events Related to Treatment of Bortezomib Combined With Y-90-ibritumomab Tiuxetan [ Time Frame: At start of treatment on days 1, 8, 15, 22 of induction, days 36 and 50 of recovery, days 1, 8, 15 of consolidation cycles for up to 3 cycles and 4 weeks after the completion of treatment. ]

    To further explore the toxicity bortezomib combined with Y-90-ibritumomab tiuxetan by collecting data on adverse events (AE) reported by patient or collected lab results that are grade 3 or grade 4 that were determined to be at least possible related to any of the studies drugs.

    Toxicity will be collected on treatment days according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:

    Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00372905


Locations
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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
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Principal Investigator: Jane Winter, MD Northwestern University

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Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00372905     History of Changes
Other Study ID Numbers: NU 05H9
STU00004871 ( Other Identifier: Northwestern University IRB )
First Posted: September 7, 2006    Key Record Dates
Results First Posted: October 17, 2018
Last Update Posted: September 4, 2019
Last Verified: October 2018
Keywords provided by Northwestern University:
follicular lymphoma
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Bortezomib
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents