Trial Outcomes & Findings for Simvastatin in Waldenstrom's Macroglobulinemia (NCT NCT00575965)

NCT ID: NCT00575965

Last Updated: 2015-12-16

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

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).

Results posted on

2015-12-16

Participant Flow

Outpatient Clinic at Dana Farber Cancer Institute

Patients with progressive nonsymptomatic disease on watch and wait were enrolled.

Participant milestones

Participant milestones
Measure
Simvastatin
Single arm, phase II study. All 18 patients received study drug.
Overall Study
STARTED
18
Overall Study
COMPLETED
18
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Simvastatin in Waldenstrom's Macroglobulinemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Simvastatin
n=18 Participants
Single arm, phase II study. All 18 patients received study drug.
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
7 Participants
n=5 Participants
Age, Categorical
>=65 years
11 Participants
n=5 Participants
Age, Continuous
66 years
STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
Sex: Female, Male
Male
13 Participants
n=5 Participants
Region of Enrollment
United States
18 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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).

Population: The analysis dataset is comprised of all evaluable patients. One patient was lost to follow-up within 3 weeks of enrollment and was unevaluable.

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.

Outcome measures

Outcome measures
Measure
Simvastatin
n=17 Participants
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 or up to 2 years.
Objective Response Rate
0.00 proportion of patients

PRIMARY outcome

Timeframe: 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).

Population: The analysis dataset is comprised of all evaluable patients. One patient was lost to follow-up within 3 weeks of enrollment and was unevaluable.

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). \[Consensus panel criteria: Weber et al, 2003; Kimby et al, 2005\].

Outcome measures

Outcome measures
Measure
Simvastatin
n=17 Participants
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 or up to 2 years.
Progression-Free Survival
6 months
Interval 2.45 to 9.55

Adverse Events

Simvastatin

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Simvastatin
n=17 participants at risk
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 or up to 2 years.
Musculoskeletal and connective tissue disorders
Elevated CPK
5.9%
1/17 • Number of events 1 • Assessed every 3 months on therapy up to day 30 post-therapy. Median duration on treatment was 6 months (range 1-24 months).
The analysis dataset is comprised of all evaluable patients. One patient was lost to follow-up within 3 weeks of enrollment and was unevaluable.
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
17.6%
3/17 • Number of events 3 • Assessed every 3 months on therapy up to day 30 post-therapy. Median duration on treatment was 6 months (range 1-24 months).
The analysis dataset is comprised of all evaluable patients. One patient was lost to follow-up within 3 weeks of enrollment and was unevaluable.

Additional Information

Steven P. Treon MD, PhD

Dana Farber Cancer Institute

Phone: 617 632 5880

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place