Clinical trial NCT00510887: Bortezomib (Velcade) With Standard Chemotherapy for Relapsed or Refractory Follicular Lymphoma
Official title: A Phase II Study of Bortezomib in Combination With Rituximab, Fludarabine, Mitoxantrone, and Dexamethasone (VR-FND) for Relapsed or Refractory Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lymphoma, Follicular
Keywords: follicular lymphoma
Velcade
VR-FND
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Millennium Pharmaceuticals, Inc.
First posted: 2007-08-02
Enrollment: 14
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: The purpose of this study is to evaluate the effectiveness and safety of combining bortezomib (Velcade) with rituximab, fludarabine, mitoxantrone, and dexamethasone in treating patients with follicular cell lymphoma.

Detailed description: This is a phase II study using the combination of bortezomib, rituximab, fludarabine, mitoxantrone and dexamethasone. The combination will given over a 28 day cycle. In addition each patient will receive Pneumocystis carinii Pneumonia (PCP) prophylaxis with Trimethoprim/sulfamethoxazole (TMP/Sulfa) or equivalent agent. On day 4 the physician has the option of starting granulocyte colony-stimulating factor (GCSF), granulocyte macrophage colony-stimulating factor (GMCSF), or pegylated GCSF.

All patients who receive at least one dose of the drug will be evaluated for toxicity. Patients will be treated with the agent for at least 2 cycles to be considered eligible for evaluation of response. The chemotherapy dosing will continue until there is evidence of disease progression, a second recurrence of unacceptable toxicity, or a maximum of 8 courses of therapy.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of grade 1-3 follicular lymphoma with persistent, relapsed, or refractory disease to at least one prior regimen.
* No prior bortezomib therapy.
* Voluntary written informed consent.
* Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control.
* Male subject agrees to use an acceptable method for contraception for the duration of the study therapy.
* 18 years of age or older.
* aspartate aminotransferase (AST),alanine aminotransferase (ALT), total bilirubin \< 3 times the upper limit of normal unless documented by the treating physician to be secondary to underlying lymphoma.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria:

* Platelet count of \< 50,000 within 14 days before enrollment unless documented by the treating physician to be due to the disease.
* Absolute neutrophil count of \< 1000 within 14 days before enrollment unless documented by the treating physician to be due to disease.
* Estimated or measured creatinine clearance of less than 30 ml/min within 14 days before enrollment.
* ≥Grade 2 peripheral neuropathy within 14 days before enrollment.
* Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.
* Patient has hypersensitivity to boron, mannitol or any drug included in the current protocol.
* Female subject is pregnant or lactating.
* Received other investigational drugs for this disease within 14 days of enrollment
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
* Known HIV+ status.
* Cardiac ejection fraction less than 35% at study entry measured by echocardiogram, Multigated Acquisition (MUGA) or cardiac MRI.

Primary outcomes:
measure: Complete and Partial Response
timeFrame: 1 year
Secondary outcomes:
measure: Duration of Response
timeFrame: up to 4 years
measure: Percentage of Subjects Experiencing Progression Free Survival
timeFrame: up to 2 years
measure: Percentage of Subjects Experiencing Overall Survival
timeFrame: up to 2 years
measure: Number of Participants With a Grade 3-4 Hematologic Toxicity.
timeFrame: up to 1 year
measure: Number of Participants With Neuropathy, Any Grade
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: David A Rizzieri, MD
role: PRINCIPAL_INVESTIGATOR
References: