Trial Outcomes & Findings for Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia (NCT NCT01807598)
NCT ID: NCT01807598
Last Updated: 2019-01-29
Results Overview
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
COMPLETED
PHASE2
10 participants
Up to 1 year
2019-01-29
Participant Flow
Participant milestones
| Measure |
Brentuximab Vedotin
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 Study
STARTED
|
10
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Brentuximab Vedotin
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 Study
Withdrawal by Subject
|
4
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Other Physician Decision
|
1
|
Baseline Characteristics
Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia
Baseline characteristics by cohort
| Measure |
Brentuximab Vedotin
n=10 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
|
Age, Continuous
|
65.8 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 1 yearPopulation: 1 of 10 participants were not evaluable due to early death during Cycle 1 (considered unrelated to study treatment)
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
Outcome measures
| Measure |
Brentuximab Vedotin
n=9 Participants
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 Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement)
|
0 participants
|
SECONDARY outcome
Timeframe: Up to 1 yearToxicity 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.
Outcome measures
| Measure |
Brentuximab Vedotin
n=10 Participants
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.
|
|---|---|
|
Brentuximab Vedotin Toxicity
Related hematologic toxicity
|
12 Related adverse events
|
|
Brentuximab Vedotin Toxicity
Related non-hematologic toxicity
|
24 Related adverse events
|
|
Brentuximab Vedotin Toxicity
Total related adverse events (toxicities)
|
36 Related adverse events
|
SECONDARY outcome
Timeframe: Baseline and up to 1 yearPopulation: CD30 marker data was not obtained for some participants.
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.
Outcome measures
| Measure |
Brentuximab Vedotin
n=8 Participants
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.
|
|---|---|
|
Percent Change of CD30 Expression on Neoplastic Mast Cells
|
-1 percentage change in CD30+ cells
Interval -62.0 to 45.0
|
SECONDARY outcome
Timeframe: Up to 1 yearThe 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.
Outcome measures
| Measure |
Brentuximab Vedotin
n=10 Participants
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.
|
|---|---|
|
Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score
Baseline (Pre-treatment)
|
36.2 score on a scale
Standard Deviation 18.1
|
|
Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score
After Treatment
|
23.6 score on a scale
Standard Deviation 15.6
|
SECONDARY outcome
Timeframe: Up to 1 yearOverall 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.
Outcome measures
| Measure |
Brentuximab Vedotin
n=10 Participants
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.
|
|---|---|
|
Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Baseline (Pre-treatment)
|
5 score on a scale
Standard Deviation 2.7
|
|
Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
After Treatment
|
2.6 score on a scale
Standard Deviation 2.7
|
SECONDARY outcome
Timeframe: Up to 1 yearPopulation: Duration of response (DOR) can not be determined if no participants had a response.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 1 yearPopulation: Time to response (TTR) can not be determined if no participants had a response.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 1 yearProgression-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
Outcome measures
| Measure |
Brentuximab Vedotin
n=10 Participants
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.
|
|---|---|
|
Progression-free Survival (PFS)
|
210 Days
Interval 77.0 to 343.0
|
Adverse Events
Brentuximab Vedotin
Serious adverse events
| Measure |
Brentuximab Vedotin
n=10 participants at risk
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.
|
|---|---|
|
Nervous system disorders
Intracranial hemorrhage
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Epiglottitis
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
10.0%
1/10 • Number of events 1 • 1 year
|
Other adverse events
| Measure |
Brentuximab Vedotin
n=10 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
30.0%
3/10 • Number of events 11 • 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
20.0%
2/10 • Number of events 3 • 1 year
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
General disorders
Fatigue
|
40.0%
4/10 • Number of events 9 • 1 year
|
|
Gastrointestinal disorders
Abdominal Pain
|
20.0%
2/10 • Number of events 4 • 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
20.0%
2/10 • Number of events 3 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
20.0%
2/10 • Number of events 2 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
2/10 • Number of events 2 • 1 year
|
|
Psychiatric disorders
Depression
|
20.0%
2/10 • Number of events 2 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
20.0%
2/10 • Number of events 3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
20.0%
2/10 • Number of events 2 • 1 year
|
|
General disorders
Infusion Related Reaction
|
20.0%
2/10 • Number of events 5 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
2/10 • Number of events 4 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
2/10 • Number of events 3 • 1 year
|
|
Gastrointestinal disorders
Ascites
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Dysphagia
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Oral pain
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
General disorders
Edema limbs
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
General disorders
Fever
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Infections and infestations
Sinusitis
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Infections and infestations
Upper respiratory infection
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Infections and infestations
Vaginal infection
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Infections and infestations
Wound infection
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
10.0%
1/10 • Number of events 2 • 1 year
|
|
Psychiatric disorders
Insomnia
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Ear and labyrinth disorders
Ear pain
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Eye disorders
Watering eyes
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.0%
1/10 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Urinary frequency
|
10.0%
1/10 • Number of events 1 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place