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Trial record 62 of 307 for:    IBRUTINIB

Ibrutinib in Treating Patients With Advanced Systemic Mastocytosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jason Robert Gotlib, Stanford University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Aggressive Systemic Mastocytosis
Mast Cell Leukemia
Systemic Mastocytosis
Intervention Drug: Ibrutinib
Enrollment 4
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Period Title: Overall Study
Started 3 1
Completed 3 1
Not Completed 0 0
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day Total
Hide Arm/Group Description

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Total of all reporting groups
Overall Number of Baseline Participants 3 1 4
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 1 participants 4 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2
  66.7%
0
   0.0%
2
  50.0%
>=65 years
1
  33.3%
1
 100.0%
2
  50.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 3 participants 1 participants 4 participants
62.6
(61.6 to 78.5)
76.8
(76.8 to 76.8)
69.7
(61.6 to 78.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 1 participants 4 participants
Female
2
  66.7%
0
   0.0%
2
  50.0%
Male
1
  33.3%
1
 100.0%
2
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 1 participants 4 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
3
 100.0%
1
 100.0%
4
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 1 participants 4 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
3
 100.0%
1
 100.0%
4
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 1 participants 4 participants
3 1 4
1.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description

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.

Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 3 1
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
2.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description 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.
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
All study participants are included in this analysis.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 3 1
Measure Type: Count of Participants
Unit of Measure: Participants
Any Adverse event
3
 100.0%
1
 100.0%
Any Grade 1 Adverse Event (mild)
3
 100.0%
1
 100.0%
Any Grade 2 Adverse Event (moderate)
3
 100.0%
1
 100.0%
Any Grade 3 Adverse Event (severe)
2
  66.7%
1
 100.0%
Any Grade 4 Adverse Event (life-threatening)
0
   0.0%
0
   0.0%
Any Grade 5 Adverse Event (death)
1
  33.3%
0
   0.0%
Any Blood or Lymphatic System Disorder
1
  33.3%
1
 100.0%
Any Gastrointestinal Disorder
1
  33.3%
1
 100.0%
Any General Disorder
3
 100.0%
1
 100.0%
Any Infection or Infestation
2
  66.7%
0
   0.0%
Any Investigations
1
  33.3%
0
   0.0%
Any Metabolism or Nutrition Disorder
1
  33.3%
1
 100.0%
Any Musculoskeletal or Connective Tissue Disorder
1
  33.3%
0
   0.0%
Any Nervous System Disorder
1
  33.3%
1
 100.0%
Any Skin or Subcutaneous Tissue Disorder
2
  66.7%
1
 100.0%
Any Vascular Disorder
1
  33.3%
0
   0.0%
3.Secondary Outcome
Title Ibrutinib Pharmacokinetics (PK)
Hide Description 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.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Change of Mast Cell Burden
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The result was only calculated for those participants for whom a post-treatment mast cell level could be determined.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 2 1
Median (Full Range)
Unit of Measure: Percent reduction of mast cells
47
(29 to 64)
0
(0 to 0)
5.Secondary Outcome
Title Serum Tryptase Levels
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Results were determined for all participants.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 3 1
Median (Full Range)
Unit of Measure: Percent reduction serum tryptase level
30
(22 to 41)
50
(50 to 50)
6.Secondary Outcome
Title Total Symptom Score (TSS)
Hide Description 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).
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Results were analyzed for all participants.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 3 1
Median (Standard Deviation)
Unit of Measure: score on a scale
Cycle 1 Day ( baseline) 56.0  (22.1) 41 [1]   (NA)
Cycle 2 Day 1 36.0  (15.0) 41 [1]   (NA)
[1]
Standard deviation can not be calculated on n=1.
7.Secondary Outcome
Title Change in Quality of Life (QoL)
Hide Description 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.
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Results were analyzed for all participants.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 3 1
Median (Standard Deviation)
Unit of Measure: score on a scale
Cycle 1 Day (baseline) 7.0  (1.0) 6.0 [1]   (NA)
Cycle 2 Day 1 7.0  (2.6) 5.0 [1]   (NA)
[1]
Standard deviation can not be calculated on n=1.
8.Secondary Outcome
Title Duration of Response (DoR)
Hide Description 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 Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Time-to-Response (TTR)
Hide Description 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 Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description 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.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 3 1
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
11.Secondary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame 26 months
Hide Outcome Measure Data
Hide Analysis Population Description
The single patient receiving ibrutinib 560 mg/day was censored per protocol.
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description:

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

Overall Number of Participants Analyzed 3 0
Mean (95% Confidence Interval)
Unit of Measure: months
16.0
(6.4 to 25.6)
Time Frame 26 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Hide Arm/Group Description

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

Ibrutinib: Given orally

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

Ibrutinib: Given orally

All-Cause Mortality
Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)      0/1 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      0/1 (0.00%)    
General disorders     
Disease progression  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Death  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Infections and infestations     
Acute hepatitis A infection  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Cryptococcal pneumonia  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Investigations     
Increased Aspartate aminotransferase (AST)  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Increased alanine aminotransferase (ALT)  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Increased total bilirubin  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Increased alkaline phosphatase  1  1/3 (33.33%)  1 0/1 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Ibrutinib 420 mg/Day Ibrutinib 560 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      1/1 (100.00%)    
Blood and lymphatic system disorders     
Anemia  1  1/3 (33.33%)  1 1/1 (100.00%)  1
Gastrointestinal disorders     
Diarrhea  1  1/3 (33.33%)  1 1/1 (100.00%)  1
Mouth sores  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Tongue sensitivity  1  0/3 (0.00%)  0 1/1 (100.00%)  1
Vomiting  1  1/3 (33.33%)  1 0/1 (0.00%)  0
General disorders     
Increased fatigue  1  3/3 (100.00%)  3 1/1 (100.00%)  1
Cold symptoms  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Edema, limbs  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Infections and infestations     
Upper respiratory infection  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Metabolism and nutrition disorders     
Hypocalcemia  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Hyponatremia  1  0/3 (0.00%)  0 1/1 (100.00%)  1
Iron total, decreased  1  0/3 (0.00%)  0 1/1 (100.00%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Nervous system disorders     
Dizziness  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Dysgeusia  1  0/3 (0.00%)  0 1/1 (100.00%)  1
Skin and subcutaneous tissue disorders     
Basal cell carcinoma, scalp  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Erythmateous rash  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Pruritus  1  0/3 (0.00%)  0 1/1 (100.00%)  1
Skin changes, fingertips  1  0/3 (0.00%)  0 0/1 (0.00%)  0
Skin lesion, forearm  1  1/3 (33.33%)  1 0/1 (0.00%)  0
Vascular disorders     
Increased flushing  1  1/3 (33.33%)  1 0/1 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Jason Robert Gotlib, MD; Professor of Medicine (Hematology)
Organization: Stanford University Medical Center
Phone: 650-498-6000
Responsible Party: Jason Robert Gotlib, Stanford University
ClinicalTrials.gov Identifier: NCT02415608     History of Changes
Other Study ID Numbers: IRB-31815
NCI-2014-02341 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HEMMPD0021 ( Other Identifier: OnCore )
P30CA124435 ( U.S. NIH Grant/Contract )
First Submitted: March 24, 2015
First Posted: April 14, 2015
Results First Submitted: May 2, 2018
Results First Posted: September 20, 2018
Last Update Posted: September 20, 2018