Waldenstrom's MacroglobulinemiaPhase 2NCT00575965
Simvastatin in Waldenstrom's Macroglobulinemia
A Phase 2 study testing Simvastatin in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
This research study seeks to find new ways to treat people with Waldenstrom's Macroglobulinemia (WM). The study is for participants with slow growing WM who otherwise might not need therapy for at least 3-6 months. Simvastatin is a drug approved by the FDA for lowering cholesterol. 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?
- Simvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Dec 2011
- 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
- 18 years of age or older
- Clinicopathological diagnosis of Waldenstrom's macroglobulinemia
- Measurable disease
- Slowly progressing disease not requiring therapy for at least 3-6 months and who do not meet consensus panel criteria for initiation of therapy
- ECOG Performance status of 0 or 1
- Adequate organ function as defined in the protocol
- Patients should agree to avoid grapefruit juice which is a major inhibitor of CYP 3A4
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than four weeks earlier
- Patients who have had rituximab within 3 months prior to entering the study
- Patients who have taken any Statin in the past
- Patients who take cyclosporin, danazol, or gemfibrozil will be excluded
- Prior history of rhabdomyolysis
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements
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- Pregnant or breastfeeding women
- HIV-positive
- Patients who take verapamil will be excluded
- Patients with active or history of liver disease
- Patients who consume more than three alcoholic beverages per day
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: Phase II Study of Simvastatin in Waldenstrom's Macroglobulinemia
This research study seeks to find new ways to treat people with Waldenstrom's Macroglobulinemia (WM). The study is for participants with slow growing WM who otherwise might not need therapy for at least 3-6 months. Simvastatin is a drug approved by the FDA for lowering cholesterol. In test tube studies the study drug appears to have direct anti-cancer effect against WM tumor cells and mast cells.
Read the detailed description
OBJECTIVES:
To define objective response, time to progression and safety of Simvastatin in Waldenström's Macroglobulinemia.
STATISTICAL DESIGN:
For this phase II study, a single-stage design is used to evaluate the efficacy of Simvastatin. With a target enrollment of 30 participants, the 95% exact confidence bounds surrounding the response estimate will be no wider than +/- 19%.
- Conditions
- Waldenstrom's Macroglobulinemia
- Being tested
- Simvastatin
- Keywords
- simvastatin
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Oral tablets taken daily
| Study group | Role | What they receive |
|---|---|---|
| Simvastatin | Experimental | Simvastatin at 20 mg daily for the first week, then dose escalated weekly by 20 mg a day to a maximum of 80 mg daily by week 4. Patients were maintained on therapy until progression. Receives: Drug: Simvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Objective response is defined as achieving partial response or better on therapy based on the Consensus Panel Recommendations from the 2nd and 3rd International Workshop on WM [Weber et al, 2003; Kimby et al, 2005]. Complete Response (CR): Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. Partial Response (PR): a >=50% reduction from baseline in the SM IgM concentration. Minor Response (MR): >=25%, but a <50% reduction of SM IgM from baseline.
Measured: Assessed at month 1 and 3 and thereafter every 3 months while on therapy. Median duration on treatment was 6 months (range 1-24 months).
Progression-Free Survival
Progression-free survival is the defined as the time from study entry to disease progression (PD) or death based on Kaplan-Meier estimates. Patients alibe without PD are censored at the date of last disease evaluation. PD is 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). [Consensus panel criteria: Weber et al, 2003; Kimby et al, 2005].
Measured: Assessed at month 1 and 3 and thereafter every 3 months while on therapy; Assessed every 6 months for up to 2 years of follow-up. Median follow-up in this study cohort was 6 months (range 2-18 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2007 (estimated)
- Study startNov 2007
- Primary completionDec 2011
- Study completionDec 2011
Why it stopped: Slow accrual led to early study termination.
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 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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Steven Treon, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00575965
- Sponsor's protocol ID
- 07-175
- Status last verified
- Nov 2015
- First submitted
- 16 Dec 2007
- Last updated
- 16 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Simvastatin in Waldenstrom's Macroglobulinemia
- ClinicalTrials.gov ID
- NCT00575965
- Acronym / sponsor ID
- 07-175
- Conditions
- Waldenstrom's Macroglobulinemia
- Keywords
- simvastatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual led to early study termination.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- Nov 2007
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 18 Dec 2007 (estimated)
- Results
- Posted 16 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study seeks to find new ways to treat people with Waldenstrom's Macroglobulinemia (WM). The study is for participants with slow growing WM who otherwise might not need therapy for at least 3-6 months. Simvastatin is a drug approved by the FDA for lowering cholesterol. In test tube studies the study drug appears to have direct anti-cancer effect against WM tumor cells and mast cells.
Detailed description
OBJECTIVES:
To define objective response, time to progression and safety of Simvastatin in Waldenström's Macroglobulinemia.
STATISTICAL DESIGN:
For this phase II study, a single-stage design is used to evaluate the efficacy of Simvastatin. With a target enrollment of 30 participants, the 95% exact confidence bounds surrounding the response estimate will be no wider than +/- 19%.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Simvastatin | Experimental | Drug: SimvastatinSimvastatin at 20 mg daily for the first week, then dose escalated weekly by 20 mg a day to a maximum of 80 mg daily by week 4. Patients were maintained on therapy until progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 18 years of age or older
- Clinicopathological diagnosis of Waldenstrom's macroglobulinemia
- Measurable disease
- Slowly progressing disease not requiring therapy for at least 3-6 months and who do not meet consensus panel criteria for initiation of therapy
- ECOG Performance status of 0 or 1
Key exclusion criteria (11 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than four weeks earlier
- Patients who have had rituximab within 3 months prior to entering the study
- Patients who have taken any Statin in the past
- Patients who take cyclosporin, danazol, or gemfibrozil will be excluded
- Prior history of rhabdomyolysis
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 |
|---|---|---|
| SimvastatinOral tablets taken daily | Drug | Simvastatin |
Primary outcome
Objective Response Rate
Time frame: Assessed at month 1 and 3 and thereafter every 3 months while on therapy. Median duration on treatment was 6 months (range 1-24 months).
Objective response is defined as achieving partial response or better on therapy based on the Consensus Panel Recommendations from the 2nd and 3rd International Workshop on WM [Weber et al, 2003; Kimby et al, 2005]. Complete Response (CR): Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. Partial Response (PR): a >=50% reduction from baseline in the SM IgM concentration. Minor Response (MR): >=25%, but a <50% reduction of SM IgM from baseline.
Progression-Free Survival
Time frame: Assessed at month 1 and 3 and thereafter every 3 months while on therapy; Assessed every 6 months for up to 2 years of follow-up. Median follow-up in this study cohort was 6 months (range 2-18 months).
Progression-free survival is the defined as the time from study entry to disease progression (PD) or death based on Kaplan-Meier estimates. Patients alibe without PD are censored at the date of last disease evaluation. PD is 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). [Consensus panel criteria: Weber et al, 2003; Kimby et al, 2005].
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Waldenstrom's Macroglobulinemia
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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 Treon, MD, PhD principal investigator
Dana-Farber Cancer Institute
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 Simvastatin in people with Waldenstrom's Macroglobulinemia, run by Dana-Farber Cancer Institute 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 7 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 16 Dec 2015. 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 16 Dec 2015). 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?
Objective Response Rate (time frame: Assessed at month 1 and 3 and thereafter every 3 months while on therapy. Median duration on treatment was 6 months (range 1-24 months).). The study lists 2 primary outcomes in all. 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 16 Dec 2015.