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Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma

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: NCT02487979
Recruitment Status : Completed
First Posted : July 2, 2015
Results First Posted : October 15, 2018
Last Update Posted : January 18, 2022
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Recurrent Osteosarcoma
Interventions Drug: Glembatumumab Vedotin
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Enrollment 22
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Glembatumumab Vedotin)
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Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Period Title: Overall Study
Started 22
Completed 1
Not Completed 21
Reason Not Completed
Physician Decision             2
Withdrawal by Subject             2
Progressive Disease             17
Arm/Group Title Treatment (Glembatumumab Vedotin)
Hide Arm/Group Description

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Overall Number of Baseline Participants 22
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants
20.09  (5.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Female
7
  31.8%
Male
15
  68.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Hispanic or Latino
3
  13.6%
Not Hispanic or Latino
19
  86.4%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   9.1%
White
20
  90.9%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants
Canada 1
United States 21
1.Primary Outcome
Title Disease Control Success
Hide Description The number of patients who do not experience disease progression or death in the six cycles following enrollment on AOST1521
Time Frame First six cycles (21-day cycle) of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Glembatumumab Vedotin)
Hide Arm/Group Description:

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
3
  13.6%
2.Secondary Outcome
Title Toxicity Associated With Chemotherapy
Hide Description The number of cycles aggregated across all patients where CTC Version 4 grade 3 or higher.
Time Frame Duration of protocol therapy - Up to two years
Hide Outcome Measure Data
Hide Analysis Population Description
22 patients were treated on protocol therapy. Sixty-one (61) cycles were reported for the analysis of toxicity.
Arm/Group Title Treatment (Glembatumumab Vedotin)
Hide Arm/Group Description:

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Overall Number of Participants Analyzed 22
Measure Type: Number
Unit of Measure: cycles
Incidence of Abdominal Pain 2
Incidence of acneiform rash 1
Incidence of Anaphylaxis 1
Incidence of Anemia 2
Incidence of Anorexia 1
Incidence of Back Pain 2
Incidence of Constipation 1
Incidence of Febrile Neutropenia 1
Incidence of Headache 1
Incidence of Hypertension 1
Incidence of Hypocalcemia 1
Incidence of Hypokalemia 4
Incidence of Hypophosphatemia 2
Incidence of Hypotension 1
Incidence of Leukopenia 1
Incidence of Lymphopenia 1
Incidence of Mucocitis 2
Incidence of Myalgia 1
Incidence of Nausea 1
Incidence of Neutropenia 2
Incidence of Pain 2
Incidence of Pneumothorax 1
Incidence of Thrombocytopenia 1
3.Secondary Outcome
Title Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life
Hide Description Total antibody and antibody-drug conjugate half-life are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion
Time Frame Baseline to 24 hours post infusion on course 1
Hide Outcome Measure Data
Hide Analysis Population Description
Samples were provided for four patients
Arm/Group Title Treatment (Glembatumumab Vedotin)
Hide Arm/Group Description:

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: hours
Total antibody half-life 35.2  (6.4)
Antibody-Drug Conjugate half-life 29.1  (8.4)
4.Secondary Outcome
Title Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance
Hide Description Total antibody and antibody-drug conjugate clearance are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion
Time Frame Baseline to 24 hours post infusion on course 1
Hide Outcome Measure Data
Hide Analysis Population Description
Samples were provided for four patients
Arm/Group Title Treatment (Glembatumumab Vedotin)
Hide Arm/Group Description:

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: millilitres per hour per kilogram
Total antibody clearance 0.8  (0.1)
Antibody-Drug Conjugate clearance 0.9  (0.3)
5.Secondary Outcome
Title Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve
Hide Description Total antibody and antibody-drug conjugate areas under the curve are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion
Time Frame Baseline to 24 hours post infusion on course 1
Hide Outcome Measure Data
Hide Analysis Population Description
Samples were provided for four patients
Arm/Group Title Treatment (Glembatumumab Vedotin)
Hide Arm/Group Description:

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: hour-microgram per millilitre
Total antibody area under the curve 2320.0  (342)
Antibody-Drug Conjugate area under the curve 2259.5  (749.6)
6.Secondary Outcome
Title Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength
Hide Description GPNMB expression by IHC of 0+ to 3+ staining strength as assessed on archived tumor specimens. 0 being no GPNMB expression and 3 indicating strong GPNMB expression.
Time Frame Prior to the time of enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was successfully completed for 19 patients
Arm/Group Title Treatment (Glembatumumab Vedotin)
Hide Arm/Group Description:

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
0+ staining strength
1
   5.3%
1+ staining strength
3
  15.8%
2+ staining strength
2
  10.5%
3+ staining strength
13
  68.4%
7.Secondary Outcome
Title RECIST Response
Hide Description The number of patients who experience a complete or partial response according the RECIST criteria for target lesions complete response (CR) disappearance of all lesions; partial response (PR ) >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.
Time Frame First six cycles (21-day cycle) of protocol therapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Glembatumumab Vedotin)
Hide Arm/Group Description:

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
1
   4.5%
Time Frame Overall protocol therapy up to 14 months in total or 18 cycles, whichever occurs first.
Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. SAE field contains NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events.
 
Arm/Group Title Treatment (Glembatumumab Vedotin)
Hide Arm/Group Description

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

All-Cause Mortality
Treatment (Glembatumumab Vedotin)
Affected / at Risk (%)
Total   14/22 (63.64%)    
Hide Serious Adverse Events
Treatment (Glembatumumab Vedotin)
Affected / at Risk (%) # Events
Total   8/22 (36.36%)    
Blood and lymphatic system disorders   
Anemia   2/22 (9.09%)  2
Febrile neutropenia   1/22 (4.55%)  1
Gastrointestinal disorders   
Abdominal pain   1/22 (4.55%)  1
Constipation   1/22 (4.55%)  1
Mucositis oral   1/22 (4.55%)  1
Nausea   1/22 (4.55%)  1
Vomiting   1/22 (4.55%)  1
General disorders   
Fever   1/22 (4.55%)  1
Pain   1/22 (4.55%)  1
Immune system disorders   
Anaphylaxis   1/22 (4.55%)  1
Investigations   
Neutrophil count decreased   1/22 (4.55%)  1
Platelet count decreased   1/22 (4.55%)  1
White blood cell decreased   1/22 (4.55%)  1
Metabolism and nutrition disorders   
Acidosis   1/22 (4.55%)  1
Hypocalcemia   1/22 (4.55%)  1
Hypokalemia   2/22 (9.09%)  2
Hypophosphatemia   1/22 (4.55%)  1
Musculoskeletal and connective tissue disorders   
Back pain   2/22 (9.09%)  2
Myalgia   1/22 (4.55%)  1
Pain in extremity   1/22 (4.55%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify   1/22 (4.55%)  1
Nervous system disorders   
Headache   1/22 (4.55%)  1
Peripheral sensory neuropathy   1/22 (4.55%)  1
Renal and urinary disorders   
Acute kidney injury   1/22 (4.55%)  1
Respiratory, thoracic and mediastinal disorders   
Pneumothorax   1/22 (4.55%)  1
Respiratory failure   1/22 (4.55%)  1
Skin and subcutaneous tissue disorders   
Rash maculo-papular   3/22 (13.64%)  3
Vascular disorders   
Hypotension   1/22 (4.55%)  1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Glembatumumab Vedotin)
Affected / at Risk (%) # Events
Total   7/22 (31.82%)    
Gastrointestinal disorders   
Mucositis oral   1/22 (4.55%)  1
Nausea   1/22 (4.55%)  1
General disorders   
Pain   1/22 (4.55%)  1
Infections and infestations   
Infections and infestations - Other, specify   1/22 (4.55%)  1
Investigations   
Lymphocyte count decreased   1/22 (4.55%)  1
Neutrophil count decreased   1/22 (4.55%)  1
Metabolism and nutrition disorders   
Anorexia   1/22 (4.55%)  1
Hypokalemia   1/22 (4.55%)  1
Hypophosphatemia   1/22 (4.55%)  1
Nervous system disorders   
Somnolence   1/22 (4.55%)  1
Skin and subcutaneous tissue disorders   
Rash acneiform   1/22 (4.55%)  1
Rash maculo-papular   2/22 (9.09%)  2
Vascular disorders   
Hypertension   1/22 (4.55%)  1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
EMail: resultsreportingcoordinator@childrensoncologygroup.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02487979    
Other Study ID Numbers: NCI-2015-01037
NCI-2015-01037 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AOST1521
s16-01136
AOST1521 ( Other Identifier: Children's Oncology Group )
AOST1521 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
First Submitted: July 1, 2015
First Posted: July 2, 2015
Results First Submitted: August 3, 2018
Results First Posted: October 15, 2018
Last Update Posted: January 18, 2022