Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia

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: NCT01807598
Recruitment Status : Completed
First Posted : March 8, 2013
Results First Posted : January 29, 2019
Last Update Posted : January 29, 2019
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Jason Robert Gotlib, Stanford University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Aggressive Systemic Mastocytosis
Mast Cell Leukemia
Systemic Mastocytosis
Intervention Drug: Brentuximab vedotin
Enrollment 10
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 10
Completed 4
Not Completed 6
Reason Not Completed
Withdrawal by Subject             4
Adverse Event             1
Other Physician Decision             1
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
<=18 years
0
   0.0%
Between 18 and 65 years
4
  40.0%
>=65 years
6
  60.0%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 10 participants
65.8
(37.8 to 81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
6
  60.0%
Male
4
  40.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
10
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
  10.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
9
  90.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants
10
1.Primary Outcome
Title Overall Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement)
Hide Description

Overall response rate (ORR) is sum of complete response (CR); partial response (PR); and clinical improvement (CI) in 1 year, ie, ORR=CR+PR+CI. The outcome is the number of participants without dispersion.

CR is following with response duration(RD) ≥12 weeks (wk)

  • No mast cell disease
  • Tryptase <20 ng/mL
  • Neutrophils ≥1x10e9/L with normal differential
  • Hemoglobin ≥11 g/dL
  • Platelets ≥100x10e9/L
  • No hepatosplenomegaly
  • No systemic mastocytosis(SM)-related organ damage PR is following with RD ≥12wk
  • Neither CR or progressive disease(PD)
  • Neoplastic mast cells reduced ≥50%
  • Tryptase reduced ≥50%
  • 1+ disease finding resolved CI is following with RD ≥12wk
  • Neither CR; PR; or PD
  • 1+ of findings above Stable disease (SD) Not CR, PR, Cl, or PD Progressive disease (PD)

Any of:

  • Worsening organ damage
  • Doubling of laboratory abnormality
  • New transfusion dependence of ≥4 units red cells or platelets at 8wk

    •+ ≥100% in transfusions for 8wk

  • 10-cm+ splenomegaly
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
1 of 10 participants were not evaluable due to early death during Cycle 1 (considered unrelated to study treatment)
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: participants
0
2.Secondary Outcome
Title Brentuximab Vedotin Toxicity
Hide Description Toxicity was assessed as the number of adverse events considered possibly, probably, or definitely-related to treatment with brentuximab vedotin. The outcome is reported as the total number of related events, a number without dispersion, and the number of related events (without dispersion) considered to be either a hematologic toxicity or non-hematologic toxicity.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: Related adverse events
Total related adverse events (toxicities) 36
Related hematologic toxicity 12
Related non-hematologic toxicity 24
3.Secondary Outcome
Title Percent Change of CD30 Expression on Neoplastic Mast Cells
Hide Description The presence of the CD30 marker (epitope) on neoplastic (cancerous) mast cells in core bone marrow biopsy samples was assessed by immunohistochemical methods, before and after brentuximab vedotin treatment. CD30 is a member of the TNF-receptor (TNF-R) superfamily, and is a transmembrane glycoprotein receptor that is normally at very low levels on the surface of activated T-cells. Overexpression of the CD30 marker is indicative of T-cell lymphoproliferative disorders and neoplastic mast cells, and the effect of a particular treatment on CD30 expression may be related to the efficacy of that treatment. The outcome is reported as the median percentage change in the level of CD30 detected, reported with full range.
Time Frame Baseline and up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
CD30 marker data was not obtained for some participants.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 8
Median (Full Range)
Unit of Measure: percentage change in CD30+ cells
-1
(-62 to 45)
4.Secondary Outcome
Title Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score
Hide Description The clinical effect of patient symptoms associated with systemic mastocytosis or mast cell leukemia were assessed with the patient-reported outcome survey entitled Myeloproliferative Neoplasm Symptom Assessment Form with Mast Cell Disorder Symptoms [(MPN-SAF(MCD)]. The MPN-SAF(MCD) is a 36-question survey, with possible responses ranged from 0 to 10, with 0 indicating not present or no effect; 1 meaning present but most favorable; and 10 meaning worst imaginable (least favorable). Total range is 0 to 360, with 0 being best possible, and 360 being worst possible. Total symptom score is calculated as the sum of the individual survey scores reported at baseline and after treatment, with lower numbers indicating less effect, and larger numbers indicated greater effect. The outcome is reported as mean score value with dispersion.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline (Pre-treatment) 36.2  (18.1)
After Treatment 23.6  (15.6)
5.Secondary Outcome
Title Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Hide Description Overall quality of life (QoL) was assessed by a single specific question from the 36-question Myeloproliferative Neoplasm Symptom Assessment Form with Mast Cell Disorder Symptoms [(MPN-SAF(MCD)] survey. Possible responses for theQoL question range from 0 to 10, with 0 indicating "as good as it can be" (most favorable), and 10 meaning "as bad as it can be" (least favorable). The QoL score was obtained at baseline and after treatment. The outcome is reported as mean score with dispersion.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline (Pre-treatment) 5  (2.7)
After Treatment 2.6  (2.7)
6.Secondary Outcome
Title Duration of Response (DOR)
Hide Description Duration of response (DOR) is defined as the time from the start of the first confirmed response until the date of the first documented and confirmed disease progression or death due to ASM or MCL. For participants with a confirmed clinical response, the outcome was to be reported as the median DOR with standard deviation.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Duration of response (DOR) can not be determined if no participants had a response.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Time to Response (TTR)
Hide Description Time to response (TTR) is defined as the time from the date of start of treatment to the date of first confirmed response. For participants with a confirmed clinical response, the outcome was to be reported as the median TTR with standard deviation.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Time to response (TTR) can not be determined if no participants had a response.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description

Progression-free survival (PFS) is defined as the time from the date of start of treatment until disease progression; death; or initiation of new therapy. The outcome is reported as the mean number of days of PFS, with 95% confidence interval.

Progressive disease (PD) is any of the following:

  • Worsening of any organ damage
  • Doubling of any laboratory abnormality
  • New transfusion dependence of ≥ 4 units red cells or platelets at 8 wk
  • ≥ 100% increase in transfusions for 8 wk
  • 10-cm+ splenomegaly
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 10
Mean (95% Confidence Interval)
Unit of Measure: Days
210
(77 to 343)
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
Brentuximab Vedotin
Affected / at Risk (%)
Total   1/10 (10.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Brentuximab Vedotin
Affected / at Risk (%) # Events
Total   4/10 (40.00%)    
Hepatobiliary disorders   
Portal vein thrombosis  1  1/10 (10.00%)  1
Nervous system disorders   
Intracranial hemorrhage  1  1/10 (10.00%)  1
Respiratory, thoracic and mediastinal disorders   
Respiratory, thoracic and mediastinal disorders - Other, Epiglottitis  1  1/10 (10.00%)  1
Pleural effusion  1  1/10 (10.00%)  1
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%
Brentuximab Vedotin
Affected / at Risk (%) # Events
Total   10/10 (100.00%)    
Blood and lymphatic system disorders   
Neutropenia  1  3/10 (30.00%)  11
Anemia  1  2/10 (20.00%)  3
Thrombocytopenia  1  1/10 (10.00%)  1
Ear and labyrinth disorders   
Ear pain  1  1/10 (10.00%)  1
Eye disorders   
Watering eyes  1  1/10 (10.00%)  1
Gastrointestinal disorders   
Abdominal Pain  1  2/10 (20.00%)  4
Constipation  1  2/10 (20.00%)  2
Diarrhea  1  2/10 (20.00%)  3
Vomiting  1  2/10 (20.00%)  3
Ascites  1  1/10 (10.00%)  1
Dysphagia  1  1/10 (10.00%)  1
Nausea  1  1/10 (10.00%)  1
Oral pain  1  1/10 (10.00%)  1
General disorders   
Fatigue  1  4/10 (40.00%)  9
Infusion Related Reaction  1  2/10 (20.00%)  5
Edema limbs  1  1/10 (10.00%)  1
Fever  1  1/10 (10.00%)  1
Infections and infestations   
Sinusitis  1  1/10 (10.00%)  1
Upper respiratory infection  1  1/10 (10.00%)  1
Vaginal infection  1  1/10 (10.00%)  1
Wound infection  1  1/10 (10.00%)  1
Metabolism and nutrition disorders   
Anorexia  1  2/10 (20.00%)  3
Dehydration  1  1/10 (10.00%)  1
Hypoalbuminemia  1  1/10 (10.00%)  2
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  1/10 (10.00%)  1
Psychiatric disorders   
Depression  1  2/10 (20.00%)  2
Insomnia  1  1/10 (10.00%)  1
Renal and urinary disorders   
Urinary frequency  1  1/10 (10.00%)  1
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/10 (20.00%)  2
Dyspnea  1  2/10 (20.00%)  2
Pleural effusion  1  1/10 (10.00%)  1
Postnasal drip  1  1/10 (10.00%)  1
Sore throat  1  1/10 (10.00%)  1
Skin and subcutaneous tissue disorders   
Rash  1  2/10 (20.00%)  4
Alopecia  1  1/10 (10.00%)  1
Dry skin  1  1/10 (10.00%)  1
Hyperhidrosis  1  1/10 (10.00%)  1
Pruritus  1  1/10 (10.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Jason R. Gotlib
Organization: Stanford University
Phone: 650-736-1253
Responsible Party: Jason Robert Gotlib, Stanford University
ClinicalTrials.gov Identifier: NCT01807598     History of Changes
Other Study ID Numbers: IRB-25727
NCI-2013-00537 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
IRB-25727 ( Other Identifier: Stanford IRB )
107011 ( Other Grant/Funding Number: Seattle Genetics )
HEMMPD0016 ( Other Identifier: OnCore )
First Submitted: March 5, 2013
First Posted: March 8, 2013
Results First Submitted: December 14, 2018
Results First Posted: January 29, 2019
Last Update Posted: January 29, 2019