Lymphoma, FollicularPhase 2NCT00510887
Bortezomib (Velcade) With Standard Chemotherapy for Relapsed or Refractory Follicular Lymphoma
A Phase 2 study testing Bortezomib, Rituximab and Fludarabine in people with Lymphoma, Follicular, run by Duke University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Follicular
- What is being tested?
- Bortezomib, Rituximab and Fludarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Sep 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Phase II Study of Bortezomib in Combination With Rituximab, Fludarabine, Mitoxantrone, and Dexamethasone (VR-FND) for Relapsed or Refractory Follicular Lymphoma
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.
Read the 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.
- Conditions
- Lymphoma, Follicular
- Being tested
- Bortezomib, Rituximab, Fludarabine, Mitoxantrone, Dexamethasone
- Keywords
- follicular lymphoma, Velcade, VR-FND
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle
RituximabDrug
Rituximab 375 mg/m2 IV on day 1
FludarabineDrug
Fludarabine 25 mg/m2 IV on days 1,2,3
MitoxantroneDrug
Also called Novantrone
Mitoxantrone 10 mg/m2 IV on day 2
DexamethasoneDrug
Dexamethasone 20 mg orally on days 1,2,3,4,5
| Study group | Role | What they receive |
|---|---|---|
| VR-FND | Experimental | 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. Receives: Drug: Bortezomib; Drug: Rituximab; Drug: Fludarabine; Drug: Mitoxantrone; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (5)
Duration of Response
Duration of response is measured from time of treatment to time of disease progression
Measured: up to 4 years
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.
Measured: up to 2 years
Percentage of Subjects Experiencing Overall Survival
Overall survival is from the day of enrollment to date of death from any cause.
Measured: up to 2 years
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).
Measured: up to 1 year
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).
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2007 (estimated)
- Study startJan 2007
- Primary completionNov 2012
- Study completionSep 2013
Why it stopped: Low accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lymphoma, FollicularStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- David A Rizzieri, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00510887
- Sponsor's protocol ID
- Pro00008487
- Other IDs
- 8785
- Status last verified
- Apr 2014
- First submitted
- 1 Aug 2007
- Last updated
- 12 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Bortezomib in Combination With Rituximab, Fludarabine, Mitoxantrone, and Dexamethasone (VR-FND) for Relapsed or Refractory Follicular Lymphoma
- ClinicalTrials.gov ID
- NCT00510887
- Acronym / sponsor ID
- Pro00008487
- Conditions
- Lymphoma, Follicular
- Keywords
- follicular lymphoma, Velcade, VR-FND
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Jan 2007
- Primary completion
- Nov 2012 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 2 Aug 2007 (estimated)
- Results
- Posted 21 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VR-FND | Experimental | Drug: Bortezomib, Drug: Rituximab, Drug: Fludarabine, Drug: Mitoxantrone, Drug: DexamethasoneBortezomib (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: VelcadeBortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle | Drug | VR-FND |
| RituximabRituximab 375 mg/m2 IV on day 1 | Drug | VR-FND |
| FludarabineFludarabine 25 mg/m2 IV on days 1,2,3 | Drug | VR-FND |
| MitoxantroneAlso: NovantroneMitoxantrone 10 mg/m2 IV on day 2 | Drug | VR-FND |
| DexamethasoneDexamethasone 20 mg orally on days 1,2,3,4,5 | Drug | VR-FND |
Primary outcome
Complete and Partial Response
Time frame: 1 year
* 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.
5 secondary outcomes
Duration of Response
Time frame: up to 4 years
Percentage of Subjects Experiencing Progression Free Survival
Time frame: up to 2 years
Percentage of Subjects Experiencing Overall Survival
Time frame: up to 2 years
Number of Participants With a Grade 3-4 Hematologic Toxicity.
Time frame: up to 1 year
Number of Participants With Neuropathy, Any Grade
Time frame: up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David A Rizzieri, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib, Rituximab and Fludarabine in people with Lymphoma, Follicular, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete and Partial Response (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2014.