Waldenstrom's MacroglobulinemiaPhase 2NCT00250926
Study of the Combination of Bortezomib, Dexamethasone, and Rituximab in Patients With Waldenstroms Macroglobulinemia
A Phase 2 study testing Bortezomib, Dexamethasone and Rituximab in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
The purpose of this study is to find out if the combination of bortezomib (Velcade), dexamethasone (Decadron) and rituximab (Rituxan) is effective in treating Waldenstrom's macroglobulinemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenstrom's Macroglobulinemia
- What is being tested?
- Bortezomib, Dexamethasone and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2005to Feb 2009
- 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
- Clinicopathological diagnosis of Waldenstrom's macroglobulinemia (WM)
- No previous therapy for WM
- Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of greater than or equal to 2 times the upper limit of each institution's normal value
- CD20 positive disease based on any previous bone marrow immuno-histochemistry or flow cytometric analysis performed up to 3 months prior to enrollment
- Karnofsky performance status > 60
- Life expectancy > 3 months
Show all 13Show fewer
- AST (SGOT) < 3 x ULN
- ALT (SGPT) < 3 x ULN
- Total bilirubin < 2 x ULN
- Calculated or measured creatinine clearance > 30mL/minute
- Serum sodium > 130 mmol/L
- 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
Who cannot join
- Previous therapy for Waldenstrom's macroglobulinemia
- Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Hypersensitivity to dexamethasone, boron or mannitol
- Pregnant or breast-feeding women
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: A Phase II Study of the Combination Bortezomib (Velcade, PS-341), Dexamethasone, and Rituximab in Patients With Waldenstroms Macroglobulinemia
The purpose of this study is to find out if the combination of bortezomib (Velcade), dexamethasone (Decadron) and rituximab (Rituxan) is effective in treating Waldenstrom's macroglobulinemia.
Read the detailed description
- This is an open-label study which means both the patient and the doctor will know what drugs and doses the patient is receiving throughout the study.
- Patients will receive 8 cycles of study treatment with bortezomib, dexamethasone and rituximab. Each cycle is 21 days long. Therapy is given on the first, fourth, eighth and eleventh day of each cycle, followed by a 10 day rest period. The first 4 cycles will be given one after the other. Three months after completing the fourth cycle of therapy, patients will receive one cycle of therapy every three months for a total of four more cycles.
- On the first, fourth, eighth and eleventh day of each cycle, the patient will receive bortezomib and dexamethasone as an intravenous injection through a needle in your vein. On the eleventh day only, the patient will also receive rituximab as an intravenous infusion after getting bortezomib and dexamethasone.
- Prior to each infusion of rituximab therapy, the patient will be asked to take some medications to prevent or reduce side effects of rituximab. These medications are benadryl, tylenol, and possibly more steroids. The doctor will determine which of these drugs are appropriate for the individual patient.
- During the rituximab infusion, the patients blood pressure and pulse will be monitored frequently and the infusion rate may be decreased depending upon the side effects experienced.
- After therapy is completed, the patient will be followed every three months for 2 more years for office visits and laboratory tests to determine how well they are doing and if the therapy continues to benefit them.
- Conditions
- Waldenstrom's Macroglobulinemia
- Being tested
- Bortezomib, Dexamethasone, Rituximab
- Keywords
- bortezomib, dexamethasone, rituximab
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Bortezomib (Velcade)
Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles
DexamethasoneDrug
Also called Dexamethasone (Decadron)
Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles
RituximabDrug
Also called Rituximab (Rituxan)
Given intravenously after bortezomib and dexamethasone on day 11 of a 21-day cycle for 8 cycles
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib, Dexamethasone, Rituximab | Experimental | A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. Receives: Drug: Bortezomib; Drug: Dexamethasone; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
This outcome measure was to assess the safety and tolerability of bortezomib, dexamethasone and rituximab in patients with untreated Waldenstroms macroglobulinemia.
Measured: 33.2 months
Response Rate
This outcome measure was to determine the response rate along with attainment of stable disease and time to disease progression following treatment with this patient population. The response rates were defined as follows.
A complete response (CR) was defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, absence of bone marrow disease by bone marrow biopsy and aspiration, and resolution of any adenopathy or splenomegaly. A near complete response (nCR) was defined as fulfilling all CR criteria in the presence of a positive immunofixation study. Patients with very good partial response (VGPR), partial response (PR), and minor response (MR) were defined as having a ≥ 90%, ≥ 50%, and 25% to 49% reduction in serum IgM levels, respectively. Progressive disease (PD) occurred when a more than 25% increase in serum IgM level or progression of clinically significant disease parameters was observed.
Measured: 33.2 months
Time to Best Response
Measured: 33.2 months
Time to Progression
Progressive Disease (PD) will be defined as a greater than 25% increase in serum IgM monoclonal protein levels from the lowest attained response value as determined by serum electrophoresis, confirmed by at least one other investigation, or progression of clinically significant disease related symptom(s).
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2005 (estimated)
- Study startOct 2005
- Primary completionMar 2007
- Study completionFeb 2009
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Waldenstrom's MacroglobulinemiaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Millennium Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Steven P. Treon, MD, MA, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00250926
- Sponsor's protocol ID
- 05-180
- Status last verified
- Mar 2016
- First submitted
- 8 Nov 2005
- Last updated
- 8 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Treon SP, Ioakimidis L, Soumerai JD, Patterson CJ, Sheehy P, Nelson M, Willen M, Matous J, Mattern J 2nd, Diener JG, Keogh GP, Myers TJ, Boral A, Birner A, Esseltine DL, Ghobrial IM. Primary therapy of Waldenstrom macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol. 2009 Aug 10;27(23):3830-5. doi: 10.1200/JCO.2008.20.4677. Epub 2009 Jun 8.
PubMed 19506160
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Combination Bortezomib (Velcade, PS-341), Dexamethasone, and Rituximab in Patients With Waldenstroms Macroglobulinemia
- ClinicalTrials.gov ID
- NCT00250926
- Acronym / sponsor ID
- 05-180
- Conditions
- Waldenstrom's Macroglobulinemia
- Keywords
- bortezomib, dexamethasone, rituximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Millennium Pharmaceuticals, Inc.
- Study start
- Oct 2005
- Primary completion
- Mar 2007 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 9 Nov 2005 (estimated)
- Results
- Posted 8 Apr 2016
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 find out if the combination of bortezomib (Velcade), dexamethasone (Decadron) and rituximab (Rituxan) is effective in treating Waldenstrom's macroglobulinemia.
Detailed description
- This is an open-label study which means both the patient and the doctor will know what drugs and doses the patient is receiving throughout the study.
- Patients will receive 8 cycles of study treatment with bortezomib, dexamethasone and rituximab. Each cycle is 21 days long. Therapy is given on the first, fourth, eighth and eleventh day of each cycle, followed by a 10 day rest period. The first 4 cycles will be given one after the other. Three months after completing the fourth cycle of therapy, patients will receive one cycle of therapy every three months for a total of four more cycles.
- On the first, fourth, eighth and eleventh day of each cycle, the patient will receive bortezomib and dexamethasone as an intravenous injection through a needle in your vein. On the eleventh day only, the patient will also receive rituximab as an intravenous infusion after getting bortezomib and dexamethasone.
- Prior to each infusion of rituximab therapy, the patient will be asked to take some medications to prevent or reduce side effects of rituximab. These medications are benadryl, tylenol, and possibly more steroids. The doctor will determine which of these drugs are appropriate for the individual patient.
- During the rituximab infusion, the patients blood pressure and pulse will be monitored frequently and the infusion rate may be decreased depending upon the side effects experienced.
- After therapy is completed, the patient will be followed every three months for 2 more years for office visits and laboratory tests to determine how well they are doing and if the therapy continues to benefit them.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib, Dexamethasone, Rituximab | Experimental | Drug: Bortezomib, Drug: Dexamethasone, Drug: RituximabA cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Clinicopathological diagnosis of Waldenstrom's macroglobulinemia (WM)
- No previous therapy for WM
- Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of greater than or equal to 2 times the upper limit of each institution's normal value
- CD20 positive disease based on any previous bone marrow immuno-histochemistry or flow cytometric analysis performed up to 3 months prior to enrollment
- Karnofsky performance status > 60
Key exclusion criteria (5 listed)
- Previous therapy for Waldenstrom's macroglobulinemia
- Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Hypersensitivity to dexamethasone, boron or mannitol
- Pregnant or breast-feeding women
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
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: Bortezomib (Velcade)Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles | Drug | Bortezomib, Dexamethasone, Rituximab |
| DexamethasoneAlso: Dexamethasone (Decadron)Given intravenously on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles | Drug | Bortezomib, Dexamethasone, Rituximab |
| RituximabAlso: Rituximab (Rituxan)Given intravenously after bortezomib and dexamethasone on day 11 of a 21-day cycle for 8 cycles | Drug | Bortezomib, Dexamethasone, Rituximab |
Primary outcome
Number of Participants With Adverse Events
Time frame: 33.2 months
This outcome measure was to assess the safety and tolerability of bortezomib, dexamethasone and rituximab in patients with untreated Waldenstroms macroglobulinemia.
Response Rate
Time frame: 33.2 months
This outcome measure was to determine the response rate along with attainment of stable disease and time to disease progression following treatment with this patient population. The response rates were defined as follows. A complete response (CR) was defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, absence of bone marrow disease by bone marrow biopsy and aspiration, and resolution of any adenopathy or splenomegaly. A near complete response (nCR) was defined as fulfilling all CR criteria in the presence of a positive immunofixation study. Patients with very good partial response (VGPR), partial response (PR), and minor response (MR) were defined as having a ≥ 90%, ≥ 50%, and 25% to 49% reduction in serum IgM levels, respectively. Progressive disease (PD) occurred when a more than 25% increase in serum IgM level or progression of clinically significant disease parameters was observed.
Time to Best Response
Time frame: 33.2 months
Time to Progression
Time frame: 42 months
Progressive Disease (PD) will be defined as a greater than 25% increase in serum IgM monoclonal protein levels from the lowest attained response value as determined by serum electrophoresis, confirmed by at least one other investigation, or progression of clinically significant disease related symptom(s).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19506160Treon SP, Ioakimidis L, Soumerai JD, Patterson CJ, Sheehy P, Nelson M, Willen M, Matous J, Mattern J 2nd, Diener JG, Keogh GP, Myers TJ, Boral A, Birner A, Esseltine DL, Ghobrial IM. Primary therapy of Waldenstrom macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol. 2009 Aug 10;27(23):3830-5. doi: 10.1200/JCO.2008.20.4677. Epub 2009 Jun 8.
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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.
Steven P. Treon, MD, MA, PhD principal investigator
Dana-Farber Cancer Institute
2 sites 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, Dexamethasone and Rituximab in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute at 2 sites 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 13 inclusion and 5 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: finished, as of the sponsor's last update on 8 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 8 Apr 2016). 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?
Number of Participants With Adverse Events (time frame: 33.2 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00250926, which also lists 1 linked publication.
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 8 Apr 2016.