Bortezomib (Velcade) With Standard Chemotherapy for Relapsed or Refractory Follicular Lymphoma

Lymphoma, Follicular Clinical Trial

Official title:

A Phase II Study of Bortezomib in Combination With Rituximab, Fludarabine, Mitoxantrone, and Dexamethasone (VR-FND) for Relapsed or Refractory Follicular Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00510887
• Other study ID #: Pro00008487
• Secondary ID: 8785
• Status: Terminated
• Phase: Phase 2
• First received: August 1, 2007
• Last updated: April 29, 2014
• Start date: January 2007
• Est. completion date: September 2013

Study information

• Verified date: April 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: September 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Bortezomib
Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle
• Rituximab
Rituximab 375 mg/m2 IV on day 1
• Fludarabine
Fludarabine 25 mg/m2 IV on days 1,2,3
• Mitoxantrone
Mitoxantrone 10 mg/m2 IV on day 2
• Dexamethasone
Dexamethasone 20 mg orally on days 1,2,3,4,5

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete and Partial Response	Complete Response: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms and normalization of biochemical abnormalities (eg. LDH) definitely assignable to follicular lymphoma.; Partial Response requires the following: greater than or equal to 50% decrease in the SPD of the 6 largest dominant nodes of nodal masses.; No increase in size of other nodes, liver, or spleen.; Splenic and hepatic nodes must regress by at least 50% in sum of the products (SPD).; Bone marrow assessment in irrelevant for determination of Partial Response since it is not measurable disease; however, if positive the type of cell should be reported.; No new lesions.	1 year	No
Secondary	Duration of Response	Duration of response is measured from time of treatment to time of disease progression	up to 4 years	No
Secondary	Percentage of Subjects Experiencing Progression Free Survival	Progression free survival is measured from treatment to progression or death, whichever comes first. Progressive disease is measured as: 50% or greater increase from nadir in the sum of the products (SPD) of any previously identified abnormal node and the appearance of any new lesions during or at the end of treatment.	up to 2 years	No
Secondary	Percentage of Subjects Experiencing Overall Survival	Overall survival is from the day of enrollment to date of death from any cause.	up to 2 years	No
Secondary	Number of Participants With a Grade 3-4 Hematologic Toxicity.	Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria (CTC).	up to 1 year	Yes
Secondary	Number of Participants With Neuropathy, Any Grade	Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria (CTC).	up to 1 year	Yes