Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02487979
• Collaborator: (none)
• Enrollment: 22
• Locations: 155
• Arm: 1
• Actual Duration (Months): 70.5
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well glembatumumab vedotin works in treating patients with osteosarcoma that has come back (recurrent) or does not respond to treatment (refractory). Monoclonal antibodies, such as glembatumumab vedotin, may find tumor cells and help kill them.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Osteosarcoma	Drug: Glembatumumab Vedotin; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate whether CDX-011 (glembatumumab vedotin) therapy either increases the disease control rate at 4 months in patients with recurrent measurable osteosarcoma as compared to an historical Children's Oncology Group (COG) experience or produces an objective response rate in patients without previous eribulin (eribulin mesylate) treatment.

SECONDARY OBJECTIVES:

1. To assess the feasibility and toxicity profile of CDX-011 in patients with recurrent osteosarcoma.

2. To describe the pharmacokinetics of CDX-011 in adolescents and young adults with recurrent osteosarcoma enrolled at COG sites and COG phase I consortium sites only.

3. To determine if there is a relationship between tumor GPNMB expression by immunohistochemistry (IHC) and response to CDX-011 therapy.

4. To estimate, in the cohort of patients previously treated with eribulin, the proportion who will experience disease progression during the first 4 months of CDX-011 therapy and the proportion of patients who experience a Response Evaluation Criteria in Solid Tumors (RECIST)-defined complete or partial response.

OUTLINE:

Patients receive glembatumumab vedotin intravenously (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.

After completion of study treatment, patients are followed up periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of GPNMB-Targeted Antibody-Drug Conjugate, CDX-011 (Glembatumumab Vedotin, CR011-vcMMAE; NSC# 763737), in Recurrent or Refractory Osteosarcoma
• Actual Study Start Date: Feb 16, 2016
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (glembatumumab vedotin) 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.	Drug: Glembatumumab Vedotin; Given IV; Other Names: Antibody-Drug Conjugate CR011-vcMMAE CDX-011 CR011-vcMMAE CR011-vcMMAE Immunotoxin ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Disease Control Success [First six cycles (21-day cycle) of protocol therapy]

   The number of patients who do not experience disease progression or death in the six cycles following enrollment on AOST1521

Secondary Outcome Measures

1. Toxicity Associated With Chemotherapy [Duration of protocol therapy - Up to two years]

   The number of cycles aggregated across all patients where CTC Version 4 grade 3 or higher.

2. Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life [Baseline to 24 hours post infusion on course 1]

   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

3. Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance [Baseline to 24 hours post infusion on course 1]

   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

4. Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve [Baseline to 24 hours post infusion on course 1]

   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

5. Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength [Prior to the time of enrollment]

   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.

6. RECIST Response [First six cycles (21-day cycle) of protocol therapy]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have had histologic verification of osteosarcoma at original diagnosis or relapse

• Patients must have measurable disease according to RECIST 1.1, and have relapsed or become refractory to conventional therapy

• Patient must have archival tumor specimen available for submission

• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

• Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea)

• Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent

• Radiation therapy (RT): >= 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation

• Monoclonal antibodies: must not have received any monoclonal based therapies within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks, prior to study enrollment

• Peripheral absolute neutrophil count (ANC) >= 1000/uL

• Platelet count >= 75,000/uL (transfusion independent)

• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

• Age 1 to < 2 years (male and female: 0.6 mg/dL)

• Age 2 to < 6 years (male and female: 0.8 mg/dL)

• Age 6 to < 10 years (male and female: 1 mg/dL)

• Age 10 to < 13 years (male and female: 1.2 mg/dL)

• Age 13 to < 16 years (male: 1.5 mg/dL and female: 1.4 mg/dL)

• Age >= 16 (male: 1.7 mg/dL and female: 1.4 mg/dL)

• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 110 U/L; for the purposes of this study the ULN for SGPT is defined as 45 U/L

• Serum albumin > 2 g/dL

• Shortening fraction of >= 27% by echocardiogram, or

• Ejection fraction of >= 50% by radionuclide angiogram

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Patients with > grade 2 neuropathy according to the Modified ("Balis") Pediatric Scale of Peripheral Neuropathies will be excluded except in cases in which neuropathy is secondary to prior surgery

• Patients who have previously received CDX-011 (CR011-vc monomethyl auristatin E [MMAE]; CDX-011) or other MMAE-containing agents

• Patients who have received other investigational drugs within 2 weeks or 5 half-lives (whichever is longer) prior to study enrollment

• Patients with a history of allergic reactions attributed to compounds of similar composition to dolastatin or auristatin; compounds of similar composition include auristatin PHE as an anti-fungal agent, auristatin PE (TZT-1027, Soblidotin, NSC-654663) as an anti-tumor agent and symplostatin 1 as an anti-tumor agent

• Patients with known central nervous system metastasis are not eligible

• Patients who have had major surgery within 2 weeks prior to enrollment are not eligible; procedures such as placement of a central vascular catheter, or limited tumor biopsy, are not considered major surgery

• Female patients who are pregnant are ineligible

• Lactating females are not eligible unless they have agreed not to breastfeed their infants

• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained

• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 2 months after the end of study treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	Banner University Medical Center - Tucson	Tucson	Arizona	United States	85719
3	University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
4	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
5	Kaiser Permanente-Anaheim	Anaheim	California	United States	92806
6	PCR Oncology	Arroyo Grande	California	United States	93420
7	Kaiser Permanente-Bellflower	Bellflower	California	United States	90706
8	Kaiser Permanente Downey Medical Center	Downey	California	United States	90242
9	Kaiser Permanente-Fontana	Fontana	California	United States	92335
10	Loma Linda University Medical Center	Loma Linda	California	United States	92354
11	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
12	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
13	Mattel Children's Hospital UCLA	Los Angeles	California	United States	90095
14	Valley Children's Hospital	Madera	California	United States	93636
15	Children's Hospital of Orange County	Orange	California	United States	92868
16	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
17	Kaiser Permanente-San Diego Zion	San Diego	California	United States	92120
18	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
19	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
20	Children's Hospital Colorado	Aurora	Colorado	United States	80045
21	University of Colorado Hospital	Aurora	Colorado	United States	80045
22	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado	United States	80218
23	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
24	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut	United States	06510
25	Yale University	New Haven	Connecticut	United States	06520
26	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
27	Kaiser Permanente-Capitol Hill Medical Center	Washington	District of Columbia	United States	20002
28	Children's National Medical Center	Washington	District of Columbia	United States	20010
29	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
30	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
31	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
32	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
33	Nicklaus Children's Hospital	Miami	Florida	United States	33155
34	AdventHealth Orlando	Orlando	Florida	United States	32803
35	Nemours Children's Hospital	Orlando	Florida	United States	32827
36	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
37	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
38	Tampa General Hospital	Tampa	Florida	United States	33606
39	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida	United States	33607
40	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
41	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
42	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
43	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
44	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
45	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
46	Carle on Vermilion	Danville	Illinois	United States	61832
47	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
48	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
49	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
50	Carle Cancer Center	Urbana	Illinois	United States	61801
51	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
52	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
53	IU Health North Hospital	Carmel	Indiana	United States	46032
54	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
55	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
56	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
57	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
58	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
59	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
60	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
61	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
62	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
63	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
64	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
65	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
66	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
67	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
68	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
69	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
70	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
71	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri	United States	63011
72	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
73	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
74	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
75	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
76	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
77	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
78	CoxHealth South Hospital	Springfield	Missouri	United States	65807
79	Mercy Hospital Washington	Washington	Missouri	United States	63090
80	Carson Tahoe Regional Medical Center	Carson City	Nevada	United States	89703
81	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
82	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
83	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
84	21st Century Oncology-Henderson	Henderson	Nevada	United States	89074
85	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
86	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
87	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
88	21st Century Oncology	Las Vegas	Nevada	United States	89109
89	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
90	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
91	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
92	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
93	21st Century Oncology-Vegas Tenaya	Las Vegas	Nevada	United States	89128
94	Ann M Wierman MD LTD	Las Vegas	Nevada	United States	89128
95	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
96	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
97	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
98	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada	United States	89135
99	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
100	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
101	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
102	21st Century Oncology-Fort Apache	Las Vegas	Nevada	United States	89148
103	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
104	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada	United States	89148
105	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
106	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
107	Renown Regional Medical Center	Reno	Nevada	United States	89502
108	Saint Mary's Regional Medical Center	Reno	Nevada	United States	89503
109	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
110	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
111	Albany Medical Center	Albany	New York	United States	12208
112	Montefiore Medical Center-Einstein Campus	Bronx	New York	United States	10461
113	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
114	Children's Hospital at Montefiore	Bronx	New York	United States	10467
115	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
116	NYU Winthrop Hospital	Mineola	New York	United States	11501
117	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
118	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
119	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
120	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
121	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
122	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
123	Dayton Children's Hospital	Dayton	Ohio	United States	45404
124	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio	United States	43606
125	Oregon Health and Science University	Portland	Oregon	United States	97239
126	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
127	Children's Oncology Group	Philadelphia	Pennsylvania	United States	19104
128	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
129	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
130	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee	United States	37067
131	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
132	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
133	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee	United States	37204
134	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
135	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
136	Medical City Dallas Hospital	Dallas	Texas	United States	75230
137	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
138	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
139	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
140	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas	United States	78229
141	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
142	University Hospital	San Antonio	Texas	United States	78229
143	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
144	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
145	Seattle Children's Hospital	Seattle	Washington	United States	98105
146	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
147	University of Washington Medical Center - Montlake	Seattle	Washington	United States	98195
148	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
149	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
150	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
151	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
152	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
153	The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Canada	H3H 1P3
154	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2
155	University Pediatric Hospital	San Juan		Puerto Rico	00926

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Lisa M Kopp, Children's Oncology Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 6, 2016

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02487979
• Other Study ID Numbers: NCI-2015-01037; NCI-2015-01037; AOST1521; s16-01136; AOST1521; AOST1521; U10CA180886
• First Posted: Jul 2, 2015
• Last Update Posted: Jan 18, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Osteosarcoma; Recurrence; Glembatumumab vedotin; Immunoconjugates; Immunotoxins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Treatment (Glembatumumab Vedotin)
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
Period Title: Overall Study
STARTED	22
COMPLETED	1
NOT COMPLETED	21

Baseline Characteristics

Arm/Group Title	Treatment (Glembatumumab Vedotin)
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 Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.09 (5.30)
Sex: Female, Male (Count of Participants)
Female	7 31.8%
Male	15 68.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 13.6%
Not Hispanic or Latino	19 86.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 9.1%
White	20 90.9%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Canada	1 4.5%
United States	21 95.5%

Outcome Measures

1. Primary Outcome

Title	Disease Control Success
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Glembatumumab Vedotin)
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
Measure Participants	22
Count of Participants [Participants]	3 13.6%

2. Secondary Outcome

Title	Toxicity Associated With Chemotherapy
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

Outcome Measure Data

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)
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
Measure Participants	22
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
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

Outcome Measure Data

Analysis Population Description

Samples were provided for four patients

Arm/Group Title	Treatment (Glembatumumab Vedotin)
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
Measure Participants	4
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
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

Outcome Measure Data

Analysis Population Description

Samples were provided for four patients

Arm/Group Title	Treatment (Glembatumumab Vedotin)
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
Measure Participants	4
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
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

Outcome Measure Data

Analysis Population Description

Samples were provided for four patients

Arm/Group Title	Treatment (Glembatumumab Vedotin)
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
Measure Participants	4
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
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

Outcome Measure Data

Analysis Population Description

Analysis was successfully completed for 19 patients

Arm/Group Title	Treatment (Glembatumumab Vedotin)
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
Measure Participants	19
0+ staining strength	1 4.5%
1+ staining strength	3 13.6%
2+ staining strength	2 9.1%
3+ staining strength	13 59.1%

7. Secondary Outcome

Title	RECIST Response
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Glembatumumab Vedotin)
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
Measure Participants	22
Count of Participants [Participants]	1 4.5%

Adverse Events

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)
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 (%)	# Events
Total	14/22 (63.6%)
Serious Adverse Events
	Treatment (Glembatumumab Vedotin)
	Affected / at Risk (%)	# Events
Total	8/22 (36.4%)
Blood and lymphatic system disorders
Anemia	2/22 (9.1%)	2
Febrile neutropenia	1/22 (4.5%)	1
Gastrointestinal disorders
Abdominal pain	1/22 (4.5%)	1
Constipation	1/22 (4.5%)	1
Mucositis oral	1/22 (4.5%)	1
Nausea	1/22 (4.5%)	1
Vomiting	1/22 (4.5%)	1
General disorders
Fever	1/22 (4.5%)	1
Pain	1/22 (4.5%)	1
Immune system disorders
Anaphylaxis	1/22 (4.5%)	1
Investigations
Neutrophil count decreased	1/22 (4.5%)	1
Platelet count decreased	1/22 (4.5%)	1
White blood cell decreased	1/22 (4.5%)	1
Metabolism and nutrition disorders
Acidosis	1/22 (4.5%)	1
Hypocalcemia	1/22 (4.5%)	1
Hypokalemia	2/22 (9.1%)	2
Hypophosphatemia	1/22 (4.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/22 (9.1%)	2
Myalgia	1/22 (4.5%)	1
Pain in extremity	1/22 (4.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1/22 (4.5%)	1
Nervous system disorders
Headache	1/22 (4.5%)	1
Peripheral sensory neuropathy	1/22 (4.5%)	1
Renal and urinary disorders
Acute kidney injury	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/22 (4.5%)	1
Respiratory failure	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	3/22 (13.6%)	3
Vascular disorders
Hypotension	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Glembatumumab Vedotin)
	Affected / at Risk (%)	# Events
Total	7/22 (31.8%)
Gastrointestinal disorders
Mucositis oral	1/22 (4.5%)	1
Nausea	1/22 (4.5%)	1
General disorders
Pain	1/22 (4.5%)	1
Infections and infestations
Infections and infestations - Other, specify	1/22 (4.5%)	1
Investigations
Lymphocyte count decreased	1/22 (4.5%)	1
Neutrophil count decreased	1/22 (4.5%)	1
Metabolism and nutrition disorders
Anorexia	1/22 (4.5%)	1
Hypokalemia	1/22 (4.5%)	1
Hypophosphatemia	1/22 (4.5%)	1
Nervous system disorders
Somnolence	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Rash acneiform	1/22 (4.5%)	1
Rash maculo-papular	2/22 (9.1%)	2
Vascular disorders
Hypertension	1/22 (4.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.