Clinical trial NCT00372905: Phase I/II Trial of VELCADE Plus Zevalin in Patients With Relapsed or Refractory Follicular Lymphoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: follicular lymphoma
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Robert H. Lurie Cancer Center
First posted: 2006-09-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) and Tolerability of Bortezomib Combined With Y-90-Ibritumomab Tiuxetan Determined by Number of Dose Limiting Toxicities in a Cohort.
timeFrame: During induction therapy, the first 28 days of treatment.
Secondary outcomes:
measure: Number of Patients With Adverse Events Related to Treatment of Bortezomib Combined With Y-90-ibritumomab Tiuxetan
timeFrame: 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.
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Jane Winter, MD
role: PRINCIPAL_INVESTIGATOR
References: