Trial Outcomes & Findings for Ibrutinib in Treating Patients With Advanced Systemic Mastocytosis (NCT NCT02415608)
NCT ID: NCT02415608
Last Updated: 2018-09-20
Results Overview
Overall response rate (ORR) is reported as the sum of the rates of participants achieving complete remission (CR), partial remission (PR), \& clinical improvement (CI). A clinical response is a response with duration of ≥ 12 weeks. CR is defined as all 4 criteria: * No presence of compact neoplastic mast cell aggregates * Serum tryptase level \< 20 ng/mL * Peripheral blood count remission defined as absolute neutrophil count (ANC) ≥1 x 10e9/L + normal differential, Hb ≥11 g/dL, \& platelet count ≥100x10e9/L * Complete resolution of palpable hepatosplenomegaly \& all biopsy-proven or suspected SM-related organ damage PR is defined as all 3 criteria with response duration ≥12 weeks, that is not CR or progressive disease: * ≥ 50% reduction in neoplastic mast cells * Serum tryptase level reduced ≥50% * Resolution of 1+ biopsy-proven or suspected systemic mastocytosis (SM)-related organ damage findings CI is defined as any improvement in any of the above measures.
TERMINATED
PHASE2
4 participants
Up to 6 months
2018-09-20
Participant Flow
Participant milestones
| Measure |
Ibrutinib 420 mg/Day
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
1
|
|
Overall Study
COMPLETED
|
3
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Ibrutinib in Treating Patients With Advanced Systemic Mastocytosis
Baseline characteristics by cohort
| Measure |
Ibrutinib 420 mg/Day
n=3 Participants
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 Participants
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Total
n=4 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
62.6 years
n=5 Participants
|
76.8 years
n=7 Participants
|
69.7 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 6 monthsOverall response rate (ORR) is reported as the sum of the rates of participants achieving complete remission (CR), partial remission (PR), \& clinical improvement (CI). A clinical response is a response with duration of ≥ 12 weeks. CR is defined as all 4 criteria: * No presence of compact neoplastic mast cell aggregates * Serum tryptase level \< 20 ng/mL * Peripheral blood count remission defined as absolute neutrophil count (ANC) ≥1 x 10e9/L + normal differential, Hb ≥11 g/dL, \& platelet count ≥100x10e9/L * Complete resolution of palpable hepatosplenomegaly \& all biopsy-proven or suspected SM-related organ damage PR is defined as all 3 criteria with response duration ≥12 weeks, that is not CR or progressive disease: * ≥ 50% reduction in neoplastic mast cells * Serum tryptase level reduced ≥50% * Resolution of 1+ biopsy-proven or suspected systemic mastocytosis (SM)-related organ damage findings CI is defined as any improvement in any of the above measures.
Outcome measures
| Measure |
Ibrutinib 420 mg/Day
n=3 Participants
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 Participants
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Overall Response Rate (ORR)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 30 daysPopulation: All study participants are included in this analysis.
Adverse events will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, and reported as the number and percentage of participants having any adverse event; by each grade of adverse event; and by affected body systems.
Outcome measures
| Measure |
Ibrutinib 420 mg/Day
n=3 Participants
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 Participants
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Number of Participants With Adverse Events
Any Adverse event
|
3 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any Grade 5 Adverse Event (death)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Any Grade 1 Adverse Event (mild)
|
3 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any Grade 2 Adverse Event (moderate)
|
3 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any Grade 3 Adverse Event (severe)
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any Grade 4 Adverse Event (life-threatening)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Any Blood or Lymphatic System Disorder
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any Gastrointestinal Disorder
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any General Disorder
|
3 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any Infection or Infestation
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Any Investigations
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Any Metabolism or Nutrition Disorder
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any Musculoskeletal or Connective Tissue Disorder
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Any Nervous System Disorder
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any Skin or Subcutaneous Tissue Disorder
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Any Vascular Disorder
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 28 daysPopulation: Because this study terminated with low total accrual, the funding sponsor elected not to analyze the samples for ibrutinib levels. There are no pharmacokinetics values on which to conduct the outcome analysis.
Plasma concentration-time profiles for each subject and mean plasma concentration-time profiles for each dose level will be plotted, plasma concentration data for ibrutinib at each time point will be summarized by descriptive statistics, and PK parameters such as maximum concentration (Cmax), minimum concentration, time at which the Cmax is reached, and area under the curve will be summarized with mean, geometric mean, medium, minimum, maximum, standard deviation, and coefficient of variation.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2 yearsPopulation: The result was only calculated for those participants for whom a post-treatment mast cell level could be determined.
The change in the number of neoplastic mast cells in tissues (blood and/or bone marrow), ie, a measure of mast cell burden, will be assessed by immunophenotyping and/or immunohistochemistry (depending on patient and disease specifics) using mast cell markers, eg, CD25, CD30, CD117, tryptase, reticulin, Wright-Giemsa staining, and/or hematoxylin-eosin staining, in peripheral blood smears or bone marrow samples. For each participant, the data are used to collectively determine a single assessment for the number of mast cells present at baseline and after treatment. The outcome is reported as the median change in that level of mast cells, with full range, from baseline up to 2 years.
Outcome measures
| Measure |
Ibrutinib 420 mg/Day
n=2 Participants
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 Participants
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Change of Mast Cell Burden
|
47 Percent reduction of mast cells
Interval 29.0 to 64.0
|
0 Percent reduction of mast cells
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Results were determined for all participants.
Serum tryptase level is a surrogate marker for the desired histopathologic response, ie, reduction in mast cell burden. Serum tryptase levels are reported as the median of the percent reduction, with full range, from baseline up to 2 years.
Outcome measures
| Measure |
Ibrutinib 420 mg/Day
n=3 Participants
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 Participants
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Serum Tryptase Levels
|
30 Percent reduction serum tryptase level
Interval 22.0 to 41.0
|
50 Percent reduction serum tryptase level
Interval 50.0 to 50.0
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Results were analyzed for all participants.
The totality of systemic mastocytosis was assessed by the total symptom score as measured by a Myeloproliferative Neoplasm Symptom Assessment Form modified for mast cell disorders \[MPN-SAF (MCD)\], and reported as the change in median score with standard deviation at baseline and 30 days. The MPN-SAF is a single, 27-question questionnaire that scores the following general measures on a scale of 0 (best) to 10 (worst): fatigue levels, effects of fatigue, satiety, pain, activity, concentration, dizziness, sleep, mood, anxiety, sexual function, itching, flushing, fever, weight loss, respiratory functions, diarrhea, lesions, and allergic reactions (some of these general terms may describe more than 1 assessment). The score on the MPN-SAF is the sum total of all 27 scores, and the range of scores is from a minimum of 0 (best; symptoms for all assessment absent) to a maximum of 270 (worst; score of 10 on all assessments).
Outcome measures
| Measure |
Ibrutinib 420 mg/Day
n=3 Participants
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 Participants
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Total Symptom Score (TSS)
Cycle 1 Day ( baseline)
|
56.0 score on a scale
Standard Deviation 22.1
|
41 score on a scale
Standard Deviation NA
Standard deviation can not be calculated on n=1.
|
|
Total Symptom Score (TSS)
Cycle 2 Day 1
|
36.0 score on a scale
Standard Deviation 15.0
|
41 score on a scale
Standard Deviation NA
Standard deviation can not be calculated on n=1.
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Results were analyzed for all participants.
The quality of life (QoL) component of the Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF) modified for mast cell symptoms, a scale of life quality ranking from 0 (best) to 10 (worst), was assessed at baseline and after 1 cycle of ibrutinib treatment (30 days), and reported as the median change in score with standard deviation.
Outcome measures
| Measure |
Ibrutinib 420 mg/Day
n=3 Participants
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 Participants
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Change in Quality of Life (QoL)
Cycle 1 Day (baseline)
|
7.0 score on a scale
Standard Deviation 1.0
|
6.0 score on a scale
Standard Deviation NA
Standard deviation can not be calculated on n=1.
|
|
Change in Quality of Life (QoL)
Cycle 2 Day 1
|
7.0 score on a scale
Standard Deviation 2.6
|
5.0 score on a scale
Standard Deviation NA
Standard deviation can not be calculated on n=1.
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: No participants achieved clinical response per protocol (minimum of any clinical improvement ≥ 12 weeks). On that basis, the overall duration of that response can not be determined.
Duration of response (DoR) was assessed through 2 years of treatment, and reported as the median with standard deviation, with response duration censored at last response assessment in the event of death or progression not documented.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2 yearsPopulation: No participants achieved clinical response per protocol (minimum of any clinical improvement ≥ 12 weeks). On that basis, the time to achieve per-protocol clinical response can not be determined.
Time-to-response (TTR) was assessed through 2 years of treatment, and reported as the median with standard deviation, censored at last response assessment in the event of death or progression not documented.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2 yearsPopulation: Results were analyzed for all participants. Values were censored at the last assessment if the participant was lost-to-follow-up or otherwise did not have a 2-year assessment.
Participants were assessed for progression-free survival (PFS) from the start of treatment through 2 years of treatment. The outcome is reported as the number of participants who were alive without disease progression after 2 years of treatment.
Outcome measures
| Measure |
Ibrutinib 420 mg/Day
n=3 Participants
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 Participants
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Progression-free Survival (PFS)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 26 monthsPopulation: The single patient receiving ibrutinib 560 mg/day was censored per protocol.
Overall survival (OS) was assessed through 2 years of treatment, and recorded as the time from the start of treatment to either progression or death, with values censored at the last response assessment if the participant did not progress or die during that period. OS is reported as reported as the median with standard deviation.
Outcome measures
| Measure |
Ibrutinib 420 mg/Day
n=3 Participants
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Overall Survival (OS)
|
16.0 months
Interval 6.4 to 25.6
|
—
|
Adverse Events
Ibrutinib 420 mg/Day
Ibrutinib 560 mg/Day
Serious adverse events
| Measure |
Ibrutinib 420 mg/Day
n=3 participants at risk
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 participants at risk
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Investigations
Increased Aspartate aminotransferase (AST)
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Investigations
Increased alanine aminotransferase (ALT)
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Investigations
Increased total bilirubin
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Investigations
Increased alkaline phosphatase
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Infections and infestations
Acute hepatitis A infection
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
General disorders
Disease progression
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Infections and infestations
Cryptococcal pneumonia
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
General disorders
Death
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
Other adverse events
| Measure |
Ibrutinib 420 mg/Day
n=3 participants at risk
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally
|
Ibrutinib 560 mg/Day
n=1 participants at risk
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
33.3%
1/3 • Number of events 1 • 26 months
|
100.0%
1/1 • Number of events 1 • 26 months
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
1/3 • Number of events 1 • 26 months
|
100.0%
1/1 • Number of events 1 • 26 months
|
|
Gastrointestinal disorders
Mouth sores
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Gastrointestinal disorders
Tongue sensitivity
|
0.00%
0/3 • 26 months
|
100.0%
1/1 • Number of events 1 • 26 months
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
General disorders
Increased fatigue
|
100.0%
3/3 • Number of events 3 • 26 months
|
100.0%
1/1 • Number of events 1 • 26 months
|
|
General disorders
Cold symptoms
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
General disorders
Edema, limbs
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • 26 months
|
100.0%
1/1 • Number of events 1 • 26 months
|
|
Metabolism and nutrition disorders
Iron total, decreased
|
0.00%
0/3 • 26 months
|
100.0%
1/1 • Number of events 1 • 26 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Nervous system disorders
Dizziness
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3 • 26 months
|
100.0%
1/1 • Number of events 1 • 26 months
|
|
Infections and infestations
Upper respiratory infection
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Skin and subcutaneous tissue disorders
Basal cell carcinoma, scalp
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Skin and subcutaneous tissue disorders
Erythmateous rash
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3 • 26 months
|
100.0%
1/1 • Number of events 1 • 26 months
|
|
Skin and subcutaneous tissue disorders
Skin changes, fingertips
|
0.00%
0/3 • 26 months
|
0.00%
0/1 • 26 months
|
|
Skin and subcutaneous tissue disorders
Skin lesion, forearm
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
|
Vascular disorders
Increased flushing
|
33.3%
1/3 • Number of events 1 • 26 months
|
0.00%
0/1 • 26 months
|
Additional Information
Jason Robert Gotlib, MD; Professor of Medicine (Hematology)
Stanford University Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place