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Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma

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ClinicalTrials.gov Identifier: NCT03436732
Recruitment Status : Terminated (Due to fatal occurrence (pneumonitis) attributed to one of the study drugs.)
First Posted : February 19, 2018
Results First Posted : November 22, 2019
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
Raffit Hassan, M.D., National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Mesothelioma
Interventions Drug: LMB-100
Drug: SEL-110
Enrollment 5
Recruitment Details  
Pre-assignment Details 1/5 participants enrolled was a screen failure following enrollment.
Arm/Group Title 140 mcg/kg LMB-100 + SEL-110 100 mcg/kg LMB-100 + SEL-110
Hide Arm/Group Description

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Period Title: Overall Study
Started 4 1
Completed 0 0
Not Completed 4 1
Reason Not Completed
Not treated-enrolled in different study             1             0
Off study after cycle 1             1             0
Adverse Event             2             0
Death             0             1
Arm/Group Title 140 mcg/kg LMB-100 + SEL-110 100 mcg/kg LMB-100 + SEL-110 Total
Hide Arm/Group Description

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Total of all reporting groups
Overall Number of Baseline Participants 4 1 5
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 1 participants 5 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
  75.0%
1
 100.0%
4
  80.0%
>=65 years
1
  25.0%
0
   0.0%
1
  20.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 1 participants 5 participants
65.75  (2.278) 58  (0) 63  (5.86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 1 participants 5 participants
Female
2
  50.0%
0
   0.0%
2
  40.0%
Male
2
  50.0%
1
 100.0%
3
  60.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 1 participants 5 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
4
 100.0%
1
 100.0%
5
 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 4 participants 1 participants 5 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
4
 100.0%
1
 100.0%
5
 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 4 participants 1 participants 5 participants
4 1 5
1.Primary Outcome
Title Number of Participants With Grade ≥3 Adverse Events Related to Study Drug at Dose Level 140 mcg/kg and 100 mcg/kg
Hide Description Here are the grade ≥3 adverse events at each dose level assessed by the Common Terminology Criteria in Adverse Events CTCAE v5.0. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is Severe or medically significant but not immediately life-threatening;hospitalization or prolongation of hospitalization indicated; disabling;limiting self care ADL (i.e., bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 is life-threatening consequences;urgent intervention indicated. Grade 5 is death related to adverse event.
Time Frame Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 140 mcg/kg 100 mcg/kg
Hide Arm/Group Description:

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Overall Number of Participants Analyzed 4 1
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 4 pericardial effusion
1
  25.0%
0
   0.0%
Grade 5 pneumonitis
0
   0.0%
1
 100.0%
2.Primary Outcome
Title Maximum Tolerated Dose (MTD)
Hide Description MTD is defined as the highest tested dose of LMB-100 and SEL-110 at which no more than 1 of 6 subjects experience a dose limiting toxicity. A dose limiting toxicity is defined as any of the following: Grade 4 neutropenia for a minimum duration of 7 days. Grade 4 thrombocytopenia (≤25.0 x 10(9) cells/L), Grade 3 thrombocytopenia associated with bleeding episodes, and Grade 4 anemia. Grade ≥3 non-hematological toxicity with the exception of Alopecia (any grade), Grade 3 nausea and vomiting lasting > 48 hours despite appropriate treatment, Grade 3 diarrhea lasting for ≤ 2 days with no fever or dehydration, and laboratory values of ≥ grade 3 that are judged not clinically significant by the investigator. Any other drug related toxicity considered significant enough to be qualified as a DLT in the opinion of the principal investigator. Inability to start cycle 2 within 3 weeks after completing cycle 1 due to drug-related adverse events.
Time Frame Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
MTD was not found because the study was closed due to a fatal occurrence of pneumonitis that was attributed to one of the study drugs.
Arm/Group Title 1/Dose Escalation
Hide Arm/Group Description:

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Number of Participants With Partial Response or Complete Response (PR + CR)
Hide Description Response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesion, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame 42 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 140 mcg/kg 100 mcg/kg
Hide Arm/Group Description:

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Overall Number of Participants Analyzed 4 1
Measure Type: Count of Participants
Unit of Measure: Participants
Partial Response
0
   0.0%
0
   0.0%
Complete Response
0
   0.0%
0
   0.0%
4.Secondary Outcome
Title Fraction of Participants With Detectable LMB-100 in Blood After Cycle 4
Hide Description Blood is measured for a detectable level of LMB-100 in the blood. LMB-100 is either detectable in the blood or not. A detectable level of LMB-100 in the blood is considered a desirable outcome for the participant. Hence, the reverse is not a considered a desirable outcome for the participant.
Time Frame Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome measure was not done because the study was closed due to a fatal occurrence of pneumonitis that was attributed to one of the study drugs.
Arm/Group Title 140 mcg/kg 100 mcg/kg
Hide Arm/Group Description:

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Number of Participants With Serious and Non-Serious Adverse Events
Hide Description Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 140 mcg/kg 100 mcg/kg
Hide Arm/Group Description:

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Overall Number of Participants Analyzed 4 1
Measure Type: Count of Participants
Unit of Measure: Participants
3
  75.0%
1
 100.0%
Time Frame Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 140 mcg/kg LMB-100 + SEL-110 100 mcg/kg LMB-100 + SEL-110
Hide Arm/Group Description

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses

LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles

SEL-110: administered on day 1 of each cycle for up to 4 cycles

All-Cause Mortality
140 mcg/kg LMB-100 + SEL-110 100 mcg/kg LMB-100 + SEL-110
Affected / at Risk (%) Affected / at Risk (%)
Total   2/4 (50.00%)      1/1 (100.00%)    
Hide Serious Adverse Events
140 mcg/kg LMB-100 + SEL-110 100 mcg/kg LMB-100 + SEL-110
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/4 (75.00%)      1/1 (100.00%)    
Cardiac disorders     
Atrial fibrillation  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Pericardial effusion  1  1/4 (25.00%)  3 0/1 (0.00%)  0
Pericardial tamponade  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Pericarditis  1  1/4 (25.00%)  1 0/1 (0.00%)  0
General disorders     
Disease progression  1  2/4 (50.00%)  2 0/1 (0.00%)  0
Infections and infestations     
Lung infection  1  0/4 (0.00%)  0 1/1 (100.00%)  1
Injury, poisoning and procedural complications     
Infusion related reaction  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Non-cardiac chest pain  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify  1 [1]  1/4 (25.00%)  1 0/1 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pneumonitis  1  0/4 (0.00%)  0 1/1 (100.00%)  2
Dyspnea  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Hypoxia  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Pleural effusion  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Pulmonary edema  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Vascular disorders     
Capillary leak syndrome  1  1/4 (25.00%)  1 0/1 (0.00%)  0
1
Term from vocabulary, CTCAE (5.0)
Indicates events were collected by systematic assessment
[1]
Death
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
140 mcg/kg LMB-100 + SEL-110 100 mcg/kg LMB-100 + SEL-110
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/4 (75.00%)      1/1 (100.00%)    
Blood and lymphatic system disorders     
Anemia  1  2/4 (50.00%)  2 1/1 (100.00%)  4
Cardiac disorders     
Sinus bradycardia  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Sinus tachycardia  1  1/4 (25.00%)  1 1/1 (100.00%)  1
Pericardial effusion  1  0/4 (0.00%)  0 1/1 (100.00%)  1
Gastrointestinal disorders     
Bloating  1  1/4 (25.00%)  1 1/1 (100.00%)  1
Constipation  1  2/4 (50.00%)  2 1/1 (100.00%)  2
Gastroesophageal reflux disease  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Hemorrhoids  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Nausea  1  1/4 (25.00%)  2 0/1 (0.00%)  0
Vomiting  1  1/4 (25.00%)  2 0/1 (0.00%)  0
Diarrhea  1  0/4 (0.00%)  0 1/1 (100.00%)  1
General disorders     
Edema face  1  1/4 (25.00%)  1 1/1 (100.00%)  1
Edema limbs  1  2/4 (50.00%)  2 1/1 (100.00%)  3
Fatigue  1  1/4 (25.00%)  1 1/1 (100.00%)  2
Fever  1  1/4 (25.00%)  1 1/1 (100.00%)  1
General disorders and administration site conditions - Other, Chest discomfort  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Localized edema  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Injury, poisoning and procedural complications     
Infusion related reaction  1  0/4 (0.00%)  0 1/1 (100.00%)  1
Investigations     
Activated partial thromboplastin time prolonged  1  1/4 (25.00%)  1 1/1 (100.00%)  1
Alanine aminotransferase increased  1  2/4 (50.00%)  3 0/1 (0.00%)  0
Alkaline phosphatase increased  1  1/4 (25.00%)  2 0/1 (0.00%)  0
Aspartate aminotransferase increased  1  3/4 (75.00%)  5 0/1 (0.00%)  0
CPK increased  1  1/4 (25.00%)  2 0/1 (0.00%)  0
Cardiac troponin I increased  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Creatinine increased  1  2/4 (50.00%)  5 0/1 (0.00%)  0
Lymphocyte count decreased  1  3/4 (75.00%)  12 1/1 (100.00%)  5
Weight gain  1  2/4 (50.00%)  2 1/1 (100.00%)  5
Weight loss  1  1/4 (25.00%)  2 0/1 (0.00%)  0
Platelet count decreased  1  0/4 (0.00%)  0 1/1 (100.00%)  1
Metabolism and nutrition disorders     
Anorexia  1  1/4 (25.00%)  1 1/1 (100.00%)  1
Hypercalcemia  1  2/4 (50.00%)  3 0/1 (0.00%)  0
Hyperglycemia  1  1/4 (25.00%)  3 1/1 (100.00%)  7
Hyperkalemia  1  2/4 (50.00%)  6 1/1 (100.00%)  1
Hypermagnesemia  1  3/4 (75.00%)  3 0/1 (0.00%)  0
Hypoalbuminemia  1  2/4 (50.00%)  9 0/1 (0.00%)  0
Hypocalcemia  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Hypokalemia  1  2/4 (50.00%)  2 1/1 (100.00%)  2
Hypomagnesemia  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Hyponatremia  1  3/4 (75.00%)  5 1/1 (100.00%)  2
Hypophosphatemia  1  0/4 (0.00%)  0 1/1 (100.00%)  2
Musculoskeletal and connective tissue disorders     
Generalized muscle weakness  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Myalgia  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Non-cardiac chest pain  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Back pain  1  0/4 (0.00%)  0 1/1 (100.00%)  1
Psychiatric disorders     
Anxiety  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Insomnia  1  2/4 (50.00%)  2 1/1 (100.00%)  1
Renal and urinary disorders     
Urine discoloration  1  0/4 (0.00%)  0 1/1 (100.00%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/4 (25.00%)  1 1/1 (100.00%)  1
Dyspnea  1  2/4 (50.00%)  2 1/1 (100.00%)  1
Pleural effusion  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Pulmonary edema  1  1/4 (25.00%)  1 0/1 (0.00%)  0
Hypoxia  1  0/4 (0.00%)  0 1/1 (100.00%)  1
Respiratory failure  1  0/4 (0.00%)  0 1/1 (100.00%)  1
Respiratory, thoracic and mediastinal disorders - Other, Hemoptysis  1  0/4 (0.00%)  0 1/1 (100.00%)  1
Skin and subcutaneous tissue disorders     
Rash maculo-papular  1  0/4 (0.00%)  0 1/1 (100.00%)  3
Vascular disorders     
Hypotension  1  1/4 (25.00%)  1 1/1 (100.00%)  3
Hypertension  1  0/4 (0.00%)  0 1/1 (100.00%)  1
1
Term from vocabulary, CTCAE (5.0)
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
Layout table for Results Point of Contact information
Name/Title: Dr. Raffit Hassan
Organization: National Cancer Institute
Phone: 240-760-6322
EMail: rh276q@nih.gov
Layout table for additonal information
Responsible Party: Raffit Hassan, M.D., National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03436732    
Other Study ID Numbers: 180057
18-C-0057
First Submitted: February 16, 2018
First Posted: February 19, 2018
Results First Submitted: September 23, 2019
Results First Posted: November 22, 2019
Last Update Posted: November 22, 2019