Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT02452554
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 62
• Locations: 69
• Arm: 1
• Actual Duration (Months): 71.6
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well lorvotuzumab mertansine works in treating younger patients with Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST), or synovial sarcoma that has returned or that does not respond to treatment. Antibody-drug conjugates, such as lorvotuzumab mertansine, are created by attaching an antibody (protein used by the body?s immune system to fight foreign or diseased cells) to an anti-cancer drug. The antibody is used to recognize tumor cells so the anti-cancer drug can kill them.

Condition or Disease	Intervention/Treatment	Phase
Pleuropulmonary Blastoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Neuroblastoma; Recurrent Rhabdomyosarcoma; Recurrent Synovial Sarcoma; Wilms Tumor	Other: Laboratory Biomarker Analysis; Biological: Lorvotuzumab Mertansine; Other: Pharmacological Study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the efficacy of IMGN901 (lorvotuzumab mertansine) in Wilms tumor, rhabdomyosarcoma, neuroblastoma and other cluster of differentiation (CD)56-expressing tumors such as pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST) and synovial sarcoma.

2. To determine the tolerability of the adult recommended phase 2 dose (RP2D) of IMGN901 administered as an intravenous infusion, administered on days 1 and 8 of a 21-day cycle, to children with refractory Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, MPNST, or synovial sarcoma.

3. To define and describe the toxicities of IMGN901 administered on this schedule.

EXPLORATORY OBJECTIVES:

1. To correlate tumor response with tumor CD56+ expression. II. To characterize the pharmacokinetics of IMGN901 in children with refractory cancer, including an assessment of impact on circulating CD56+ peripheral blood cells.

OUTLINE:

Patients receive lorvotuzumab mertansine intravenously (IV) over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of IMGN901 (Lorvotuzumab Mertansine; NSC#: 783609) in Children With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor (MPNST) and Synovial Sarcoma
• Actual Study Start Date: Oct 12, 2015
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Sep 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (lorvotuzumab mertansine) Patients receive lorvotuzumab mertansine IV over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Lorvotuzumab Mertansine; Given IV; Other Names: Anti-Human NCAM-1 Monoclonal Antibody N901 BB-10901 huN901-DM1 IMGN901 ; Other: Pharmacological Study; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Objective Response by Response Evaluation Criteria in Solid Tumors Version 1.1 [Up to 18 weeks (6 courses)]

   The best response of disease will be examined separately in each stratum. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and Clopper-Pearson confidence intervals will be constructed.

2. Incidence of Toxicities of Lorvotuzumab Mertansine, Using the NCI Common Terminology Criteria for Adverse Events Version 4.0 [Up to 12 months (17 courses)]

   Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade for toxicities with Possible, Probable, or Definite attribution to the study drug. Tables will summarize incidence by cycle.

Other Outcome Measures

1. Pharmacokinetic (PK) Parameters of Lorvotuzumab Mertansine [Pre-treatment, end of infusion, and 2, 6, 24, 48, and 96 hours after end of infusion on day 1 of course 1, and pre-treatment, end of infusion, and 2 and 6 hours after end of infusion on day 8 of course 1]

   A descriptive analysis of PK parameters of lorvotuzumab mertansine will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). Analyses will be descriptive and exploratory and hypotheses generating in nature.

2. CD56 Expression [Day 1 and 8 of course 1 prior to lorvotuzumab mertansine]

   The association between CD56+ expression and response will be evaluated using the exact conditional test of proportions (Fisher?s Exact test). Analyses will be descriptive and exploratory and hypotheses generating in nature.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse

• Primary strata

• Wilms tumor

• Rhabdomyosarcoma

• Neuroblastoma

• Secondary strata: miscellaneous CD56-expressing tumors:

• Pleuropulmonary blastoma

• Malignant peripheral nerve sheath tumor (MPNST)

• Synovial sarcoma

• Patients must have radiographically measurable disease (with the exception of those with neuroblastoma)

• Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)

• Note: the following do not qualify as measurable disease:

• Malignant fluid collections (e.g., ascites, pleural effusions)

• Bone marrow infiltration except that detected by metaiodobenzylguanidine (MIBG) scan for neuroblastoma

• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted in patients with neuroblastoma who do not have measurable disease but have MIBG-avid evaluable disease

• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)

• Previously radiated lesions that have not demonstrated clear progression post radiation

• Leptomeningeal lesions that do not meet the measurements noted above

• Patients with neuroblastoma who do not have measurable disease but have MIBG-avid evaluable disease are eligible

• Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

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

• Patients must have received standard treatment appropriate for their tumor type

• Myelosuppressive chemotherapy: patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)

• Hematopoietic growth factors: at least 14 days must have elapsed after receiving pegfilgrastim and least 7 days must have elapsed since the completion of therapy with a non-pegylated growth factor

• Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur

• Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody

• Radiotherapy: >= 2 weeks must have elapsed since local palliative external beam radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; >= 3 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given

• Stem cell transplant or rescue without TBI: no evidence of active graft vs. host disease and >= 2 months must have elapsed since transplant

• For patients with solid tumors without bone marrow involvement: peripheral absolute neutrophil count (ANC) >= 1000/uL

• For patients with solid tumors without bone marrow involvement: platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)

• For patients with solid tumors and known bone marrow metastatic disease: peripheral absolute neutrophil count (ANC) >= 750/uL

• For patients with solid tumors and known bone marrow metastatic disease: platelet count >= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

• 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: maximum serum creatinine: 0.6 mg/dL in males and females

• Age 2 to < 6 years: maximum serum creatinine: 0.8 mg/dL in males and females

• Age 6 to < 10 years: maximum serum creatinine: 1 mg/dL in males and females

• Age 10 to < 13 years: maximum serum creatinine: 1.2 mg/dL in males and females

• Age 13 to < 16 years: maximum serum creatinine: 1.5 mg/dL in males and 1.4 mg/dL in females

• Age >= 16 years: maximum serum creatinine: 1.7 mg/dL in males and 1.4 mg/dL in females

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

• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)

• Serum albumin >= 2 g/dL

• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study

• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

• 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 who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 4 weeks after the last dose of study therapy; breastfeeding women are excluded

• Concomitant medications

• Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible

• Patients who have received previous treatment with IMGN901 are not eligible

• Investigational drugs: patients who are currently receiving another investigational drug are not eligible

• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible

• Anti-graft-versus-host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial

• Patients who have a CNS toxicity > grade 2 are not eligible

• Patients must not have known active central nervous system (CNS) metastases; patients with known central nervous system metastases are excluded unless treated surgically or with radiotherapy, and stable with no recurrent lesions for at least 6 months

• Patients who have baseline peripheral neuropathy >= grade 2 are not eligible

• Patients who have an uncontrolled infection are not eligible

• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
3	Kaiser Permanente Downey Medical Center	Downey	California	United States	90242
4	Loma Linda University Medical Center	Loma Linda	California	United States	92354
5	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
6	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609-1809
7	Children's Hospital of Orange County	Orange	California	United States	92868
8	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
9	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
10	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
11	Children's Hospital Colorado	Aurora	Colorado	United States	80045
12	Yale University	New Haven	Connecticut	United States	06520
13	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
14	Children's National Medical Center	Washington	District of Columbia	United States	20010
15	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
16	Nicklaus Children's Hospital	Miami	Florida	United States	33155
17	AdventHealth Orlando	Orlando	Florida	United States	32803
18	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
19	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
20	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
21	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
22	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
23	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
24	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
25	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
26	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
27	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
28	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
29	Eastern Maine Medical Center	Bangor	Maine	United States	04401
30	Maine Children's Cancer Program	Scarborough	Maine	United States	04074
31	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
32	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
33	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
34	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
35	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
36	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
37	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
38	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
39	Mayo Clinic	Rochester	Minnesota	United States	55905
40	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
41	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
42	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
43	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
44	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
45	Mount Sinai Hospital	New York	New York	United States	10029
46	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
47	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
48	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
49	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
50	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
51	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
52	Oregon Health and Science University	Portland	Oregon	United States	97239
53	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
54	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
55	Prisma Health Richland Hospital	Columbia	South Carolina	United States	29203
56	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
57	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
58	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
59	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
60	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
61	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
62	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
63	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
64	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
65	Seattle Children's Hospital	Seattle	Washington	United States	98105
66	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
67	West Virginia University Healthcare	Morgantown	West Virginia	United States	26506
68	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
69	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: James I Geller, Children's Oncology Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 9, 2018

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT02452554
• Other Study ID Numbers: ADVL1522; NCI-2015-00746; ADVL1522; ADVL1522; ADVL1522; U10CA180886
• First Posted: May 22, 2015
• Last Update Posted: Jan 13, 2022
• Last Verified: Jan 1, 2022

• Additional relevant MeSH terms: Neoplasms; Sarcoma; Neuroblastoma; Rhabdomyosarcoma; Wilms Tumor; Sarcoma, Synovial; Nerve Sheath Neoplasms; Neurofibrosarcoma; Pulmonary Blastoma; Recurrence; Maytansine; Lorvotuzumab mertansine; Ado-Trastuzumab Emtansine

Study Results

Participant Flow

Recruitment Details	Each of 6 disease strata enrolled up to 16 patients who were evaluable for the primary response criteria.

Arm/Group Title	Stratum 1: Wims Tumor	Stratum 2: Rhabdomyosarcoma	Stratum 3: Neuroblastoma	Stratum 4: Pleuropulmonary Blastoma	Stratum 5: Malignant Peripheral Nerve Sheath Tumor	Stratum 6: Synovial Sarcoma
Arm/Group Description	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles
Period Title: Overall Study
STARTED	17	17	12	1	5	10
COMPLETED	0	0	1	0	0	1
NOT COMPLETED	17	17	11	1	5	9

Baseline Characteristics

Arm/Group Title	Stratum 1: Wims Tumor	Stratum 2: Rhabdomyosarcoma	Stratum 3: Neuroblastoma	Stratum 4: Pleuropulmonary Blastoma	Stratum 5: Malignant Peripheral Nerve Sheath Tumor	Stratum 6: Synovial Sarcoma	Total
Arm/Group Description	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	Total of all reporting groups
Overall Participants	17	17	12	1	5	10	62
Age (Count of Participants)
<=18 years	13 76.5%	7 41.2%	12 100%	1 100%	5 100%	6 60%	44 71%
Between 18 and 65 years	4 23.5%	10 58.8%	0 0%	0 0%	0 0%	4 40%	18 29%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	12.61 (6.48)	18.43 (5.28)	7.78 (1.94)	3.69 (NA)	12.96 (4.29)	17.37 (4.59)	13.2 (6.37)
Sex: Female, Male (Count of Participants)
Female	5 29.4%	8 47.1%	3 25%	1 100%	4 80%	6 60%	27 43.5%
Male	12 70.6%	9 52.9%	9 75%	0 0%	1 20%	4 40%	35 56.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 11.8%	3 17.6%	1 8.3%	0 0%	1 20%	1 10%	8 12.9%
Not Hispanic or Latino	13 76.5%	14 82.4%	10 83.3%	1 100%	4 80%	9 90%	51 82.3%
Unknown or Not Reported	2 11.8%	0 0%	1 8.3%	0 0%	0 0%	0 0%	3 4.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 5.9%	0 0%	0 0%	0 0%	1 20%	0 0%	2 3.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 11.8%	3 17.6%	1 8.3%	0 0%	1 20%	2 20%	9 14.5%
White	10 58.8%	14 82.4%	10 83.3%	1 100%	3 60%	5 50%	43 69.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	4 23.5%	0 0%	1 8.3%	0 0%	0 0%	3 30%	8 12.9%

Outcome Measures

1. Primary Outcome

Title	Objective Response by Response Evaluation Criteria in Solid Tumors Version 1.1
Description	The best response of disease will be examined separately in each stratum. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and Clopper-Pearson confidence intervals will be constructed.
Time Frame	Up to 18 weeks (6 courses)

Outcome Measure Data

Analysis Population Description

2 participants were excluded from analysis; 1 participant never received treatment and 1 participant was ineligible, also never receiving treatment.

Arm/Group Title	Stratum 1: Wims Tumor	Stratum 2: Rhabdomyosarcoma	Stratum 3: Neuroblastoma	Stratum 4: Pleuropulmonary Blastoma	Stratum 5: Malignant Peripheral Nerve Sheath Tumor	Stratum 6: Synovial Sarcoma
Arm/Group Description	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles
Measure Participants	16	16	12	1	5	10
Number (95% Confidence Interval) [Percent of participants]	0.00 0%	6.25 36.8%	0.00 0%	0.00 0%	0.00 0%	0.00 0%

2. Primary Outcome

Title	Incidence of Toxicities of Lorvotuzumab Mertansine, Using the NCI Common Terminology Criteria for Adverse Events Version 4.0
Description	Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade for toxicities with Possible, Probable, or Definite attribution to the study drug. Tables will summarize incidence by cycle.
Time Frame	Up to 12 months (17 courses)

Outcome Measure Data

Analysis Population Description

203 treatment-cycles were reported for the analysis. 2 participants were excluded from analysis;1 participant never received treatment and 1 participant was ineligible, also never receiving treatment.

Arm/Group Title	Treatment (Lorvotuzumab Mertansine)
Arm/Group Description	Patients receive lorvotuzumab mertansine IV over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lorvotuzumab Mertansine: Given IV Pharmacological Study: Correlative studies
Measure Participants	60
Measure Treatment Cycles	203
Anemia: Grade 2	0
Anemia: Grade 3	2
Anemia: Grade 4	0
Anemia: Grade 5	0
Colonic fistula: Grade 2	0
Colonic fistula: Grade 3	0
Colonic fistula: Grade 4	1
Colonic fistula: Grade 5	0
Colonic perforation: Grade 2	0
Colonic perforation: Grade 3	0
Colonic perforation: Grade 4	0
Colonic perforation: Grade 5	1
Dental caries: Grade 2	0
Dental caries: Grade 3	1
Dental caries: Grade 4	0
Dental caries: Grade 5	0
Nausea: Grade 2	0
Nausea: Grade 3	1
Nausea: Grade 4	0
Nausea: Grade 5	0
Vomiting: Grade 2	1
Vomiting: Grade 3	1
Vomiting: Grade 4	0
Vomiting: Grade 5	0
Tooth infection: Grade 2	0
Tooth infection: Grade 3	1
Tooth infection: Grade 4	0
Tooth infection: Grade 5	0
Alanine aminotransferase increased: Grade 2	0
Alanine aminotransferase increased: Grade 3	3
Alanine aminotransferase increased: Grade 4	0
Alanine aminotransferase increased: Grade 5	0
Aspartate aminotransferase increased: Grade 2	0
Aspartate aminotransferase increased: Grade 3	1
Aspartate aminotransferase increased: Grade 4	0
Aspartate aminotransferase increased: Grade 5	0
Lymphocyte count decreased: Grade 2	0
Lymphocyte count decreased: Grade 3	2
Lymphocyte count decreased: Grade 4	0
Lymphocyte count decreased: Grade 5	0
Hyperglycemia: Grade 2	0
Hyperglycemia: Grade 3	1
Hyperglycemia: Grade 4	0
Hyperglycemia: Grade 5	0
Hyperuricemia: Grade 2	0
Hyperuricemia: Grade 3	1
Hyperuricemia: Grade 4	0
Hyperuricemia: Grade 5	0
Hypokalemia: Grade 2	0
Hypokalemia: Grade 3	1
Hypokalemia: Grade 4	0
Hypokalemia: Grade 5	0
Hypophosphatemia: Grade 2	0
Hypophosphatemia: Grade 3	1
Hypophosphatemia: Grade 4	0
Hypophosphatemia: Grade 5	0
Headache: Grade 2	1
Headache: Grade 3	0
Headache: Grade 4	0
Headache: Grade 5	0
Peripheral motor neuropathy: Grade 2	0
Peripheral motor neuropathy: Grade 3	1
Peripheral motor neuropathy: Grade 4	0
Peripheral motor neuropathy: Grade 5	0
Peripheral sensory neuropathy: Grade 2	0
Peripheral sensory neuropathy: Grade 3	1
Peripheral sensory neuropathy: Grade 4	0
Peripheral sensory neuropathy: Grade 5	0
All Reportable AEs: Grade 2	2
All Reportable AEs: Grade 3	18
All Reportable AEs: Grade 4	1
All Reportable AEs: Grade 5	1

3. Other Pre-specified Outcome

Title	Pharmacokinetic (PK) Parameters of Lorvotuzumab Mertansine
Description	A descriptive analysis of PK parameters of lorvotuzumab mertansine will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). Analyses will be descriptive and exploratory and hypotheses generating in nature.
Time Frame	Pre-treatment, end of infusion, and 2, 6, 24, 48, and 96 hours after end of infusion on day 1 of course 1, and pre-treatment, end of infusion, and 2 and 6 hours after end of infusion on day 8 of course 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	CD56 Expression
Description	The association between CD56+ expression and response will be evaluated using the exact conditional test of proportions (Fisher?s Exact test). Analyses will be descriptive and exploratory and hypotheses generating in nature.
Time Frame	Day 1 and 8 of course 1 prior to lorvotuzumab mertansine

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	While patients were on Protocol Therapy: Up to 17, 28-day cycles
Adverse Event Reporting Description	AE reporting is collected routinely using case report forms. The SAE table reflects NCI CTCAEs submitted by the institution, via expedited reporting (NCI AdEERs/CAeRs). The "AE Other" table reflects all CTCAEs collected; excludes those reported as SAEs. Patients who did not receive treatment before being take off study were not included in the AE tables; per protocol, AE data was not collected for those patients. Ineligible patients were excluded from both the AE and All-Cause Mortality tables.
Arm/Group Title	Stratum 1: Wims Tumor		Stratum 2: Rhabdomyosarcoma		Stratum 3: Neuroblastoma		Stratum 4: Pleuropulmonary Blastoma		Stratum 5: Malignant Peripheral Nerve Sheath Tumor		Stratum 6: Synovial Sarcoma
Arm/Group Description	ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles		ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles		ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles		ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles		ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles		ADVL1522 Dose Level 1: IMGN901 110 mg/m2/IV over 1-1.5 hours on Days 1 and 8 every 21 days, repeatable up to 17 cycles
All Cause Mortality
	Stratum 1: Wims Tumor		Stratum 2: Rhabdomyosarcoma		Stratum 3: Neuroblastoma		Stratum 4: Pleuropulmonary Blastoma		Stratum 5: Malignant Peripheral Nerve Sheath Tumor		Stratum 6: Synovial Sarcoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/17 (58.8%)		11/16 (68.8%)		4/12 (33.3%)		1/1 (100%)		1/5 (20%)		2/10 (20%)
Serious Adverse Events
	Stratum 1: Wims Tumor		Stratum 2: Rhabdomyosarcoma		Stratum 3: Neuroblastoma		Stratum 4: Pleuropulmonary Blastoma		Stratum 5: Malignant Peripheral Nerve Sheath Tumor		Stratum 6: Synovial Sarcoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/16 (43.8%)		8/16 (50%)		1/12 (8.3%)		0/1 (0%)		0/5 (0%)		3/10 (30%)
Eye disorders
Optic nerve disorder	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Gastrointestinal disorders
Abdominal pain	2/16 (12.5%)		2/16 (12.5%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Colonic fistula	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Colonic perforation	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Dental caries	0/16 (0%)		0/16 (0%)		1/12 (8.3%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Nausea	0/16 (0%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		1/10 (10%)
Vomiting	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		2/10 (20%)
General disorders
Death NOS	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Pain	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Infections and infestations
Sepsis	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Tooth infection	0/16 (0%)		0/16 (0%)		1/12 (8.3%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Investigations
Alanine aminotransferase increased	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		1/10 (10%)
Aspartate aminotransferase increased	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Creatinine increased	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Metabolism and nutrition disorders
Dehydration	0/16 (0%)		2/16 (12.5%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Hypercalcemia	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Hyperuricemia	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Hypokalemia	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/16 (6.3%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	2/16 (12.5%)		2/16 (12.5%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Tumor pain	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Nervous system disorders
Headache	0/16 (0%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		1/10 (10%)
Renal and urinary disorders
Acute kidney injury	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Hypoxia	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Pleural effusion	3/16 (18.8%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	Stratum 1: Wims Tumor		Stratum 2: Rhabdomyosarcoma		Stratum 3: Neuroblastoma		Stratum 4: Pleuropulmonary Blastoma		Stratum 5: Malignant Peripheral Nerve Sheath Tumor		Stratum 6: Synovial Sarcoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/16 (31.3%)		4/16 (25%)		4/12 (33.3%)		1/1 (100%)		1/5 (20%)		4/10 (40%)
Blood and lymphatic system disorders
Anemia	2/16 (12.5%)		0/16 (0%)		1/12 (8.3%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Gastrointestinal disorders
Abdominal pain	0/16 (0%)		0/16 (0%)		0/12 (0%)		1/1 (100%)		0/5 (0%)		0/10 (0%)
Nausea	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
General disorders
Fatigue	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Fever	0/16 (0%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		1/10 (10%)
Non-cardiac chest pain	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Infections and infestations
Catheter related infection	0/16 (0%)		0/16 (0%)		1/12 (8.3%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Investigations
Alanine aminotransferase increased	0/16 (0%)		0/16 (0%)		1/12 (8.3%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Lymphocyte count decreased	0/16 (0%)		3/16 (18.8%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		2/10 (20%)
Weight loss	0/16 (0%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		1/5 (20%)		0/10 (0%)
Metabolism and nutrition disorders
Anorexia	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Dehydration	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		1/1 (100%)		0/5 (0%)		0/10 (0%)
Hyperglycemia	0/16 (0%)		0/16 (0%)		1/12 (8.3%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Hyperkalemia	0/16 (0%)		0/16 (0%)		1/12 (8.3%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Hyponatremia	0/16 (0%)		0/16 (0%)		0/12 (0%)		1/1 (100%)		0/5 (0%)		0/10 (0%)
Hypophosphatemia	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/16 (0%)		0/16 (0%)		0/12 (0%)		1/1 (100%)		0/5 (0%)		0/10 (0%)
Nervous system disorders
Peripheral motor neuropathy	0/16 (0%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		1/10 (10%)
Peripheral sensory neuropathy	0/16 (0%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		1/10 (10%)
Reproductive system and breast disorders
Irregular menstruation	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/16 (0%)		0/16 (0%)		0/12 (0%)		1/1 (100%)		0/5 (0%)		0/10 (0%)
Dyspnea	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		1/1 (100%)		0/5 (0%)		0/10 (0%)
Hypoxia	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Pleural effusion	0/16 (0%)		1/16 (6.3%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)
Vascular disorders
Hypertension	1/16 (6.3%)		0/16 (0%)		0/12 (0%)		0/1 (0%)		0/5 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Must obtain prior sponsor approval.