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

NCT00372905 | Terminated Phase 1 Results DMC

• 2 other identifiers: NU 05H9STU00004871
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Lymphoma

Keywords

follicular lymphoma

Outcome Measures

Primary Outcomes (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.

  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.

  During induction therapy, the first 28 days of treatment.

Secondary Outcomes (1)

• Number of Patients With Adverse Events Related to Treatment of Bortezomib Combined With Y-90-ibritumomab Tiuxetan

  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.

Study Arms (1)

bortezomib, Ibritumomab tiuxetan, rituximab

EXPERIMENTAL

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; Drug: bortezomib; Drug: Ibritumomab tiuxetan

Interventions

rituximab DRUG

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.

Also known as: Rituxan, IDEC-C2B8

bortezomib, Ibritumomab tiuxetan, rituximab

bortezomib DRUG

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.

Also known as: Velcade

bortezomib, Ibritumomab tiuxetan, rituximab

Ibritumomab tiuxetan DRUG

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.

Also known as: 111-indium-ibritumomab tiuxetan, Y-90-ibritumomab tiuxetan

bortezomib, Ibritumomab tiuxetan, rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• Robert H. Lurie Cancer Center: collaborator

Study Sites (2)

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular

Interventions

Rituximab; Bortezomib; ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The study closed permanently due to slow accrual with only 17 patients treated on study. This was before the expected accrual goal of 24 patients

Results Point of Contact

• Title: Jane Winter, MD
• Organization: Northwestern University

Jwinter@nm.org

312 695 4033

Study Officials

• Jane Winter, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2006
• First Posted: September 7, 2006
• Study Start: July 24, 2007
• Primary Completion: June 22, 2010
• Study Completion: July 8, 2013
• Last Updated: September 4, 2019
• Results First Posted: October 17, 2018

Record last verified: 2018-10

Locations

US (2)