Clinical trial NCT00369707: Trial of VELCADE and Rituxan as Front-line Tx for Low-grade NHL
Official title: A Phase II Trial of Combination Bortezomib and Rituximab as Front-line Therapy for Low-grade Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Hodgkin's Lymphoma
Keywords: Non-Hodgkin's Lymphoma
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Robert H. Lurie Cancer Center
First posted: 2006-08-29
Enrollment: 42
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 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.

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 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

Primary outcomes:
measure: Overall Response Rate (Complete Response and Partial Response) After Three Inductions Cycles of Treatment.
timeFrame: At baseline and at the completion of 3 cycles of treatment where 1 cycle equals 35 days.
Secondary outcomes:
measure: Overall Response Rate After 1 Course of Induction Therapy
timeFrame: At baseline and at the completion of cycle 1 (1 cycle =35 days)
measure: Overall Response Rate After Completion of Maintenance Therapy
timeFrame: At baseline and every 2 months during treatment of up to 3 cycles of induction (1 cycle =35days) and 4 cycles of maintenance (1 cycle =2 months) for up to 12 months.
measure: Duration of Overall Response
timeFrame: Every 2 months for up to 12 months then every 6 months for 2 years and annually for 1 year
measure: Number of Patients That Experience Adverse Events With Bortezomib/Rituximab Combination Treatment
timeFrame: Day 1 of each cycle and at the completion of cycles 1 and 3, during treatment up to 12 months
measure: Tissue Evaluation
timeFrame: At baseline and at response assessment 1 after induction part A, 2, after induction part B and 3, maintenance period.
measure: Correlation of Tumor Burden
timeFrame: At the start of treatment and at Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS and OS for all patients is reported at 4 years.
measure: Percentage of Patients With Treatment Failure
timeFrame: Median follow up for all patients was 50 months and on intent to treat, TTF rate for all patients is reported at 4 years.
measure: Progression Free Survival (PFS) Rate
timeFrame: Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS for all patients is reported at 4 years.
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
city: Chicago
country: United States
facility: Hematology-Oncology Associates of Illinois
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
Study officials:
affiliation: Northwestern University
name: Andrew M. Evens, DO, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Evens AM, Smith MR, Lossos IS, Helenowski I, Millenson M, Winter JN, Rosen ST, Gordon LI. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-Hodgkin lymphoma: a multicentre phase II study. Br J Haematol. 2014 Aug;166(4):514-20. doi: 10.1111/bjh.12915. Epub 2014 Apr 25.