Ibrutinib in Treating Patients With Advanced Systemic Mastocytosis
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|ClinicalTrials.gov Identifier: NCT02415608|
Recruitment Status : Terminated (Slow accrual)
First Posted : April 14, 2015
Results First Posted : September 20, 2018
Last Update Posted : September 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Aggressive Systemic Mastocytosis Mast Cell Leukemia Systemic Mastocytosis||Drug: Ibrutinib||Phase 2|
Evaluate the response rate to ibrutinib in patients with advanced systemic mastocytosis (SM) (aggressive systemic mastocytosis [ASM] or mast cell leukemia [MCL], or SM-associated hematologic non-mast cell disorder [AHNMD]) by the end of 6 cycles (6 months).
- Evaluate the tolerability and safety profile of ibrutinib in patients with advanced SM.
- Evaluate the pharmacokinetic (PK) profile of ibrutinib in a subset of patients with advanced SM.
- Evaluate changes in histopathology (blood and bone marrow) of patients with advanced SM in response to ibrutinib therapy.
- Evaluate changes in mastocytosis related symptom scores and quality-of-life (QOL) using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF).
- Evaluate the duration of response (DoR) and time to response (TTR).
- Evaluate progression-free survival (PFS) and overall survival.
Patients receive ibrutinib orally (PO) once daily (QD) on days 1 to 28. Treatment repeats every 28 days for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients achieving an unconfirmed or confirmed clinical improvement (CI), partial response (PR), or complete response (CR) by the end of course 6 will be permitted to continue maintenance courses of ibrutinib on an ongoing basis until loss of response/progressive disease, or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Ibrutinib in Advanced Systemic Mastocytosis|
|Study Start Date :||March 2015|
|Actual Primary Completion Date :||November 4, 2016|
|Actual Study Completion Date :||June 14, 2017|
Experimental: Ibrutinib 420 mg/day
Participants receive ibrutinib daily on days 1 to 28, at 420 mg/day in 28-day cycles
Given orally in 28-day cycles
Experimental: Ibrutinib 560 mg/day
Participants receive ibrutinib daily on days 1 to 28, at 560 mg/day in 28-day cycles
Given orally in 28-day cycles
- Overall Response Rate (ORR) [ Time Frame: Up to 6 months ]
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.
- Number of Participants With Adverse Events [ Time Frame: 30 days ]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.
- Ibrutinib Pharmacokinetics (PK) [ Time Frame: 28 days ]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.
- Change of Mast Cell Burden [ Time Frame: 2 years ]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.
- Serum Tryptase Levels [ Time Frame: 2 years ]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.
- Total Symptom Score (TSS) [ Time Frame: 30 days ]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).
- Change in Quality of Life (QoL) [ Time Frame: 30 days ]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.
- Duration of Response (DoR) [ Time Frame: 2 years ]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.
- Time-to-Response (TTR) [ Time Frame: 2 years ]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.
- Progression-free Survival (PFS) [ Time Frame: 2 years ]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.
- Overall Survival (OS) [ Time Frame: 26 months ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02415608
|United States, California|
|Stanford University Hospitals and Clinics|
|Stanford, California, United States, 94305|
|Principal Investigator:||Jason Gotlib||Stanford University Hospitals and Clinics|