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

Primary Purpose

Lymphoma, Follicular

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bortezomib
Rituximab
Fludarabine
Mitoxantrone
Dexamethasone
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Follicular focused on measuring follicular lymphoma, Velcade, VR-FND

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Duke University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

VR-FND

Arm Description

Bortezomib (VELCADER) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab. Each cycle will be repeated every 28 days for 8 cycles maximum.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Duration of Response
Duration of response is measured from time of treatment to time of disease progression
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.
Percentage of Subjects Experiencing Overall Survival
Overall survival is from the day of enrollment to date of death from any cause.
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).
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).

Full Information

First Posted
August 1, 2007
Last Updated
April 29, 2014
Sponsor
Duke University
Collaborators
Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00510887
Brief Title
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

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Terminated
Why Stopped
Low accrual.
Study Start Date
January 2007 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Follicular
Keywords
follicular lymphoma, Velcade, VR-FND

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
VR-FND
Arm Type
Experimental
Arm Description
Bortezomib (VELCADER) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab. Each cycle will be repeated every 28 days for 8 cycles maximum.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab 375 mg/m2 IV on day 1
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine 25 mg/m2 IV on days 1,2,3
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Other Intervention Name(s)
Novantrone
Intervention Description
Mitoxantrone 10 mg/m2 IV on day 2
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone 20 mg orally on days 1,2,3,4,5
Primary Outcome Measure Information:
Title
Complete and Partial Response
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Duration of Response
Description
Duration of response is measured from time of treatment to time of disease progression
Time Frame
up to 4 years
Title
Percentage of Subjects Experiencing Progression Free Survival
Description
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.
Time Frame
up to 2 years
Title
Percentage of Subjects Experiencing Overall Survival
Description
Overall survival is from the day of enrollment to date of death from any cause.
Time Frame
up to 2 years
Title
Number of Participants With a Grade 3-4 Hematologic Toxicity.
Description
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).
Time Frame
up to 1 year
Title
Number of Participants With Neuropathy, Any Grade
Description
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).
Time Frame
up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A Rizzieri, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

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

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