Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles

Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles

Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Ibrutinib: Given orally

Ibrutinib 420 mg/Day

Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Ibrutinib: Given orally

Ibrutinib 560 mg/Day

Total

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

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.

Overall Response Rate (ORR)

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.

Number of Participants With Adverse Events

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.

Ibrutinib Pharmacokinetics (PK)

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.

Change of Mast Cell Burden

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.

Serum Tryptase Levels

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).

Total Symptom Score (TSS)

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.

Change in Quality of Life (QoL)

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.

Duration of Response (DoR)

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.

Time-to-Response (TTR)

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.

Progression-free Survival (PFS)

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.

Overall Survival (OS)

Overall Study

Jason Robert Gotlib, MD; Professor of Medicine (Hematology)

Aggressive Systemic Mastocytosis

Mast Cell Leukemia

Systemic Mastocytosis

Ibrutinib

Stanford University Hospitals and Clinics

Ibrutinib in Treating Patients With Advanced Systemic Mastocytosis

A Phase 2 Study of Ibrutinib in Advanced Systemic Mastocytosis

Jason Robert Gotlib

Principal Investigator

National Cancer Institute (NCI)

Subjects will receive two doses of Omalizumab while hospitalized, followed by continued outpatient therapy, every 2 to 4 weeks, for up to 6 months.

Subjects will receive two doses of placebo while hospitalized, followed by continued outpatient therapy, every 2 to 4 weeks, for up to 6 months.

Omalizumab

Placebo

To determine if treatment with omalizumab over 6 months will produce a reduction in the number and timing of anaphylactic events in subjects with a history of frequent idiopathic anaphylaxis. Ordinal outcome of participants based on number of events in 6 months after baseline and timing of first event. Events were calculated based on detailed event logs maintained by the patients and collected every 2-4 weeks based on injection schedule. Mean percent change in number of events experienced while on study agent for each subject and results presented as a group.

Reduction in the Number and Timing of Anaphylactic Events in Subjects With a History of Frequent Idiopathic Anaphylaxis.

Carter, Melody

Anaphylaxis

Hypotension

Bronchospasm

Angioedema

Epinephrine

Omalizumab (Xolair)

Placebos

National Institutes of Health Clinical Center, 9000 Rockville Pike

A Randomized, Double-Blind, Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis

A Randomized Double-Blinded, Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis

National Institute of Allergy and Infectious Diseases (NIAID)

Idiopathic Anaphaylaxis

Drug Anaphylaxis

Venom Anaphylaxis

Food Anaphylaxis

Cause of Unexplained Anaphylaxis

Studies in the Pathogenesis of Anaphylaxis

The primary objective of this study is to determine if patients with anaphylaxis (IA or SA) have clinical &amp; laboratory features that correlate with genetic or molecular abnormalities in their mast cell population including the presence of clonal mast cell disease.

Explore abnormalities in signaling Evaluate growth and degranulation of mast cells grown in vitro. Identify patients with the D816Vmutation

mastocytosis/vomiting

Ibrutinib in Treating Patients With Advanced Systemic Mastocytosis

A Randomized, Double-Blind, Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis

Cause of Unexplained Anaphylaxis

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